Reproduction trait plays an important role in pig production. Identification of molecular markers that are linked to litter size may contribute to the genetic development of porcine reproduction traits. In this study,...Reproduction trait plays an important role in pig production. Identification of molecular markers that are linked to litter size may contribute to the genetic development of porcine reproduction traits. In this study, porcine ring finger protein 4 （pRNF4） and Matrix metalloproteinase 9 （pMMP-9） were selected as candidate genes on the basis of their physiological roles in reproduction. Two single-nucleotide polymorphisms （416C〉T in pRNF4 and - 1257G〉A in pMMP-9） that could be detected by PCR restriction fragment length polymorphism （PCR-RFLP） were discovered and tested for statistical associations with litter size traits in three populations. For 416C〉T, TT genotype was associated with a significantly higher （p〈0.05） number of live births than those recorded for CC sows and the additive effect was significant （p〈0.05） in Qingping and Min Pigs populations in later parities. For -1257G〉A, inconsistent results were found in three populations. The results suggested that T allele in pRNF4 gene might confer a high prolificacy in breeding and further studies were needed to confLrm the results.展开更多
The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan,oxidized by CYP3A4 to produce inactive compounds,is used for treatment o...The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan,oxidized by CYP3A4 to produce inactive compounds,is used for treatment of various cancers including advanced non small cell lung cancer (NSCLC) patients. CYP3A4*16B polymorphism was associated with decreased metabolism of irrinotecan. Irinotecan is also metabolized by carboxylesterase to its principal active metabolite,SN-38,which is subsequently glucuronidated by UGT1As to form the inactive compound SN-38G. UGT1A1*28 and UGT1A1*6 polymorphisms were useful for predicting severe toxicity with NSCLC patients treated with irinotecan-based chemotherapy. Platinum-based compounds (cisplatin,carboplatin) are being used in combination with new cytotoxic drugs such as gemcitabine,paclitaxel,docetaxel,or vinorelbine in the treatment of advanced NSCLC. Cisplatin activity is mediated through the formation of cisplatin-DNA adducts. Gene polymorphisms of DNA repair factors are therefore obvious candidates for determinants of repair capacity and chemotherapy efficacy. ERCC1,XRCC1 and XRCC3 gene polymorphisms were a useful marker for predicting better survival in advanced NSCLC patients treated with platinum-based chemotherapy. XPA and XPD polymorphisms significantly increased response to platinum-based chemotherapy. These DNA repair gene polymorphisms were useful as a predictor of clinical outcome to the platinum-based chemotherapy. EGFR kinase inhibitors induce dramatic clinical responses in NSCLC patients with advanced disease. EGFR gene polymorphism in intron 1 contains a polymorphic single sequence dinucleotide repeat (CA-SSR) showed a statistically significant correlation with the gefitinib response and was appeared to be a useful predictive marker of the development of clinical outcome containing skin rashes with gefitinib treatment. The other polymorphisms of EGFR were also associated with increased EGFR promoter activity. EGFR gene mutations and polymorphisms were also associated with EGFR kinase inhibitors response and toxicity.展开更多
OBJECTIVE To evaluate the association between DNA(cytosine-5)-methyltransferase 3 alpha(DNMT3A)genetic polymorphisms and the disease prognosis of R882 mutation negative acute myeloid leukemia(AML)patients.METHODS DNMT...OBJECTIVE To evaluate the association between DNA(cytosine-5)-methyltransferase 3 alpha(DNMT3A)genetic polymorphisms and the disease prognosis of R882 mutation negative acute myeloid leukemia(AML)patients.METHODS DNMT3A 11 SNPs(rs11695471,rs2289195,rs734693,rs2276598,rs1465825,rs7590760,rs13401241,rs7581217,rs749131,rs41284843 and rs7560488)were genotyped using a MassA RRAY platform or Sanger sequencing method in 317 diagnostic non-FABM3 AML patients without R882 mutation from southern China.AML patients underwent combined chemotherapy with cytarabine and anthracyclines.Overall survival(OS)and Disease-free survival(DFS)as major end points were defined.The prognostic(median OS and DFS)evaluations were performed by Kaplan-Meier curve and Cox′s proportional hazard model.RESULTS We found that the rs2289195 G>A SNP could act as a poor prognostic predictor independently(HR=0.442,P=0.035 for OS;HR=0.431,P=0.031 for DFS),while the rs1465825 T>C SNP and rs7590760 G>C SNP appeared to predict independently poor prognosis for both OS(HR=1.453,P=0.037 for rs1465825;HR=1.584,P=0.063 for rs7590760)and DFS(HR=1.459,P=0.057 for rs1465825;HR=1.965,P=0.017for rs7590760).However,no significant associations between other DNMT3A polymorphisms and prognosis(OS in conjunction with DFS)were observed.CONCLUSION DNMT3A polymorphisms may be potential predictive markers for AML prognosis in R882 mutation negative patients,which might improve prognostic stratification of AML.展开更多
In order to further study functions of the porcine myostatin gene, we analyzed the polymorphisms of porcine myostatin gene in promoter region among different breeds including Yorkshire, Landrace, Duroc, Junmu, Min pig...In order to further study functions of the porcine myostatin gene, we analyzed the polymorphisms of porcine myostatin gene in promoter region among different breeds including Yorkshire, Landrace, Duroc, Junmu, Min pig and Sanjiang white pig by PCR-RFLPs. The allele T dominated in the imported lean-type pig breeds such as Yorkshire, Landrace and Duroc. No allele A was detected in Junmu and Sanjiang white pig, and the frequencies of three genotypes were about equal in Min pig. The result using X2 analysis showed that the distribution of three genotypes was related to pig breeds.展开更多
Three breeds of sows were observed to investigate the relationship between Single Nucleotide Polymorphisms（SNPs） in Mu Opioid Receptor（MOR）and stereotypic behaviour,such as,sham-chewing,bar biting and standing sti...Three breeds of sows were observed to investigate the relationship between Single Nucleotide Polymorphisms（SNPs） in Mu Opioid Receptor（MOR）and stereotypic behaviour,such as,sham-chewing,bar biting and standing still in order to better understand the mechanism of stereotypic development of the animals in restrained conditions.MOR exon 2 partial sequences were amplified to analyze single nucleotide polymorphisms by PCR-SSCP.One SNP,a silence mutant was found.A significant difference （P〈0.01）was found in the frequency of genotypes in these 3 breeds where only the BB genotype,which was identical to that published in GenBank,was found in the Duroc breed,while no AA genotype was found in Landrace,3 genotypes AA,BB and AB were found in Yorkshire.The result also indicated that the individuals with AA and AB genotypes tended to be more active in sham-chewing than those with the BB genotype（P〈0.05）.The overall results of this study suggested that sham-chewing of sows may be subjected to both genetic control and environmental conditions,but activity level was more likely to be affected by their environment.We can putatively draw the conclusion that MOR gene has effect on the sham-chewing behavioral traits of sow.展开更多
The short tandem repeat (STR) markers are widely used in human identification and paternity testing in the field of forensic genetics[1].Recent researches on polymorphic STRs have led to their applications to populati...The short tandem repeat (STR) markers are widely used in human identification and paternity testing in the field of forensic genetics[1].Recent researches on polymorphic STRs have led to their applications to population genetics,forensic DNA database,human individual identification,paternity testing,genetic mapping,disease linkage analysis,archaeology and potential inference of the ethnic origin of an individual[2].展开更多
The cytochrome P450 2El （ CYP2E1 ） and aldehyde dehydrogenase 2 （ALDH2） have been demonstrated that they were related to the development of hepatocellular carcinoma （HCC）. However, the associations have not been...The cytochrome P450 2El （ CYP2E1 ） and aldehyde dehydrogenase 2 （ALDH2） have been demonstrated that they were related to the development of hepatocellular carcinoma （HCC）. However, the associations have not been explained conclusively, and the combined analysis with the CYP2E1 Rsa I polymorphism and the ALDH2 pol- ymorphism have not been clarifed. In this study, we performed a meta-analysis to interpret the association between CYP2E1 and ALDH2 polymorphisms and HCC risk. Published literatures were retrieved from PubMed and Embase up to July, 2014. The pooled odds ratio （OR） with 95% confidence interval （CI） was calculated by using fixed- effects or random-effects model. A total of twelve case-controlled studies with 1 077 cancer cases and 2 000 controls concerning the CYP2E1 polymorphism were selected for this meta-analysis. The results indicated that there was no significantly associations between CYP2E1 polymorphism and risk of HCC （cl/c2 vs el/el ： OR - 1.11, 95% CI： 0.88-=1.39, P-0.38; c2/c2 vs el/el. OR -0.90, 95% CI. 0.54-=1.50, P-0.69; cl/c2 ＋ c2/c2 vs el/ el ： OR - 1.07, 95% CI： 0.89 -~ 1.30, P -0.47）. Further analysis of subgroup based on the ethnicity also showed no statistically significant associated with risk of HCC between the East Asians and the Europeans. In addi- tion, eight studies including 911 cases and 1 903 controls were included in this meta-analysis about the association between ALDH2 polymorphism and HCC risk. Results Based on our study also showed no significant association between ALDH2 polymorphism and the risk of HCC risk （ ＊ 1/＊ 2 vs ＊ 1/＊ 1： OR -0. 92, 95% CI： 0.65 -＊ 1.32, P-0.66; ,2/,2 vs ＊ 1/＊ 1. OR -0.82, 95% CI. 0.57-=1.18, P-0.28, ＊ 1/,2 ＋ ,2/,2 vs ＊ 1/＊ 1 ： OR -0.90, 95% CI. 0. 63 -- 1.29, P -0. 57）. The present meta-analysis indicated that there was no sig- nificant association between CYP2E1 polymorphism or ALDH2 polymorphism and HCC risk in the East Asians and the Europeans.展开更多
OBJECTIVE The purpose of the present study was to investigate the impact of fluvas.tatin formulation on the pharmacokinetics-genetic polymorphis relationship.METHODS We compared the difference between the pharmacokine...OBJECTIVE The purpose of the present study was to investigate the impact of fluvas.tatin formulation on the pharmacokinetics-genetic polymorphis relationship.METHODS We compared the difference between the pharmacokinetics of fluvastatin as an extended-release(ER) 80 mg tablet and an immediate-release(IR) 40 mg capsule in terms of drug metabolism enzyme and transporter ge.netic polymorphisms.In this open-label,randomized,two-period,two-treatment,crossover study,ef.fects of BCRP,SLCO1B1,MDR1,CYP2C9,and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed in 24 healthy individuals.Each treatment duration was 7 days with a washout period of 7 days between the crossover.Serum concentration of fluvastatin was evaluated using highperformance liquid chromatography-tandem mass spectrometry.RESULTS The SLCO1 B1 T521 C genotype had no statistically significant effect on IR 40 mg capsule of fluvastatinafter single or repeated doses.However,for the ER 80 mg tablet,the SLCO1 B1 T521 C genotype correlated with the AUC_(0-24) of repeat doses(P=0.01).The CYP2C9*3 genotype correlated with the AUC_(0-24) after the first dose IR40 mg capsule(P<0.05);however,the difference between CYP2C9*1/*1 and CYP2 C9*1/*3 was not statistically significant after repeated doses.CONCLUSION The effect of SLCO1B1T521C on fluvas.tatin exposure was observed and was more profound in ER and repeated dose administration than in IR and single dose administration.We recommend that formulation should be incorporated into future pharmacogenomics studies and clinical implication guidelines.展开更多
The BRCA1 Associated RING Domain(BARD1) gene has been identified as a high penetrance gene for breast cancer, whose germline and somatic mutations were reported in both non-BRCA1/2 hereditary site-specific and sporadi...The BRCA1 Associated RING Domain(BARD1) gene has been identified as a high penetrance gene for breast cancer, whose germline and somatic mutations were reported in both non-BRCA1/2 hereditary site-specific and sporadic breast cancer cases. BARD1 plays a crucial role in tumor repression, along with its heterodimeric partner BRCA1. In the current study, we tested the hypothesis that common non-synonymous polymorphisms in BARD1 are associated with breast cancer susceptibility in a case-control study of 507 patients with incident breast cancer and 539 frequency-matched cancer-free controls in Chinese women. We genotyped all three common(minor allele frequency (MAF) > 0.10) non-synonymous polymorphisms(Pro24Ser, Arg378Ser, and Val507Met) in BARD1. We found that the BARD1 Pro24Ser variant genotypes(24Pro/Ser and 24Ser/Ser) and Arg378Ser variant homozygote 378Ser/Ser were associated with a significantly decreased breast cancer risk, compared with their wild-type homozygotes, respectively. Furthermore, a significant locus-locus interaction was evident between Pro24Ser and Arg378Ser (P-int = 0.032). Among the 378Ser variant allele carriers, the 24Pro/Pro wild-type homozygote was associated with a significantly increased breast cancer risk (adjusted OR = 1.81, 95% CI = 1.11-2.95), but the subjects having 24Pro/Ser or Ser/Ser variant genotypes had a significantly decreased risk(adjusted OR = 0.74, 95% CI = 0.56-0.99). In stratified analysis, this locus-locus interaction was more evident among subjects without family cancer history, those with positive estrogen receptor (ER) and individuals with negative progesterone receptor(PR). These findings indicate that the potentially functional polymorphisms Pro24Ser and Arg378Ser in BARD1 may jointly contribute to the susceptibility of breast cancer.展开更多
Aim:In this study,we would like to determine associations between β2-Adrenergic Receptor(β2AR)polymorphisms at codon 16 and 27 and the response to short acting β2-agonist during asthmatic exacerbation.Methods:This ...Aim:In this study,we would like to determine associations between β2-Adrenergic Receptor(β2AR)polymorphisms at codon 16 and 27 and the response to short acting β2-agonist during asthmatic exacerbation.Methods:This was a prospective cross-sectional study of one year duration.One hundred and thirty two asthmatic patients were recruited.Five mls of venous blood was taken for DNA extraction and then genotyped for the β2AR polymorphisms using multiplex PCR.Patient's clinical responses to β2-agonist nebulization were then compared to their genotype to determine the association.Results:We found that there was no association between β2AR polymorphisms at both codon 16 and 27 with response towards short acting β2-agonist,P=0.315 and P=0.706 respectively.Conclusion:We suggested that β2AR polymorphisms at both codon 16 and 27 had no influent on the response to short acting β2-agonist.展开更多
Herein,a first example of energetic-energetic cocrystal polymorphs with a 1:1 M ratio was discovered by cocrystallizing CL-20(2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane)with 1,3-DNP(1,3-dinitropyrazole...Herein,a first example of energetic-energetic cocrystal polymorphs with a 1:1 M ratio was discovered by cocrystallizing CL-20(2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane)with 1,3-DNP(1,3-dinitropyrazole).These two energetic cocrystal polymorphs(cocrystal 1 and cocrystal 2)exhibit distinct crystal packing styles,which lead to significant variations in their physicochemical properties.Notably,cocrystal 2 has a high density of 1.963 g·cm^(-3)at 170 K,exhibiting high detonation performances(9187 m·s^(-1);38.68 GPa)comparable to HMX(1,3,5,7-tetranitro-1,3,5,7-tetrazocane)meanwhile displaying an improved safety(10 J)relative to RDX(1,3,5-trinitro-1,3,5-triazinane),making it a potential high-energy,low-sensitivity energetic material.This work opens up a new strategy to deeply tune properties of energetic materials by constructing energetic-energetic cocrystal polymorphs.These energetic cocrystal polymorphs represent a new field of energetic materials that has not yet been studied.展开更多
A seeding strategy was developed in the preparation of cyclotetramethylenetetranitramine(HMX)explosive micro-particles by solvent-antisolvent method, to control their polymorphs from dangerous gamma(y) type to the des...A seeding strategy was developed in the preparation of cyclotetramethylenetetranitramine(HMX)explosive micro-particles by solvent-antisolvent method, to control their polymorphs from dangerous gamma(y) type to the desired and standard beta(β) form with the size distribution of <10.0 μm, by using a low concentration of β-HMX fine particles as micro-seed in the antisolvent medium. All products were characterized by X-ray diffraction(XRD), scanning electron microscopy(SEM), and dynamic light scattering particle size analyzer. In the next step, the effective factors on the sizes and morphologies of micro-particles in the presence and absence of two soft templates of poly(ethylene glycol)-400(PEG-400) polymer and coconut fatty acid diethanolamide(lauramide) surfactant were investigated. The results of experiments showed that using of water-soluble PEG-400 in the low antisolvent temperatures leads to the production of very spherical particles. Also non-ionic surfactant of lauramide, direct the crystal growth to needle-like structures. The advantages of this method are its capability for the simple production of β-HMX micro-particles in the large scale production process, with the various crystal structures and particles size distributions.展开更多
The follicle stimulating hormone beta-subunit （FSHβ） gene plays an important role in piglets. Marker-assisted selection （MAS） in conjunction with traditional selection methods is most effective for improving the ...The follicle stimulating hormone beta-subunit （FSHβ） gene plays an important role in piglets. Marker-assisted selection （MAS） in conjunction with traditional selection methods is most effective for improving the piglets breeding traits. To find the new SNPs, the polymorphism of it in six pig breeds （Min, Landrace, Yorkshine, Duroc, wild boar, and wild boar × Landrace） was analyzed by using PCR-SSCP and was further compared with each other. Polymorphism was found and the sequencing results showed that there was one silent mutation on exon2 （C48T） and two mutations on exon3 （T422C and A514G）. Genotype distribution of FSHβ in Min and wild boar on exon3 was in accordance with Hardy-Weinberg Law.展开更多
Based on chicken＇ consensus map issued in 2000, 17 microsatellites near 4 candidate genes such as IGF2, OBR, GDF8 and APOA 1 in 4 chromosomes （chromosome 5, 7, 8 and 24） were chosen for polymorphism analysis and co...Based on chicken＇ consensus map issued in 2000, 17 microsatellites near 4 candidate genes such as IGF2, OBR, GDF8 and APOA 1 in 4 chromosomes （chromosome 5, 7, 8 and 24） were chosen for polymorphism analysis and construction of linkage map. Combining the technique of PCR and the fluorescent semi-automated detection, genome scanning was performed for 440 chickens, which was derived from China Agricultural University chicken resource families within three generations. The individuals of this resource families were genotyped. The results showed that the number of alleles ranged from 4 to 14; heterozygosity （H） of markers was between 0.3116 and 0.9148. Polymorphic information content （PIC） varied from 0.2672 to 0.8679. Microsatellites along with above-mentioned 4 candidate genes doing as general markers were used to construct linkage map. The spans of 4 linkage maps constructed in the part region of chromosome 5, 7, 8 and 24 were 263.5, 79.9, 206.2 and 104.2 cM, respectively. The order of markers was consistent with that of counterpart of reported consensus map. However, The spans of linkage map were larger than that of consensus map. The constructed linkage maps laid the foundation for mapping quantitative trait loci （QTL） responsible for economically important traits in chicken.展开更多
Background and objective:Lung cancer is one of the malignant tumors.Gene mutations associated with cellular immune function and regulating the activation and proliferation of immune cells.Several publications have exp...Background and objective:Lung cancer is one of the malignant tumors.Gene mutations associated with cellular immune function and regulating the activation and proliferation of immune cells.Several publications have explored the relationship between cytotoxic T lymphocyte antigen-4(CTLA-4)+49 adenine(A)/guanine(G)polymorphism and susceptibility of lung cancer,but the results remain controversial.Thus,we performed this meta-analysis to derive a more comprehensive estimation of the relationship.Methods:All articles addressed lung cancer and polymorphisms of CTLA-4 were searched from the Pub Med,EMBASE databases published up to June 29,2019.Odds ratios(ORs)with 95%confidence intervals(CIs)were used to assess the strength of association.Publication bias of relevant studies was examined via Begg’s test and funnel plots.Results:The meta-analysis included 8 case-control studies covering 4,430 lung cancer patients and 5,198 healthy controls from September 2008 to April 2020.The overall eligible data indicated that CTLA-4+49 A/G polymorphisms did not correlate with the elevated lung cancer risk in all genetic comparison models(dominant model:OR=1.037,95%CI:0.925-1.161;recessive model:OR=0.968,95%CI:0.888-1.055;allele model:OR=0.992,95%CI:0.933-1.054;homozygous model:OR=0.980,95%CI:0.857-1.121;heterozygous model:OR=1.023,95%CI:0.906-1.154).In further stratified analyses,CTLA-4+49 A/G polymorphism was found to be significantly associated with susceptibility to NSCLC in these models(dominant model:OR=1.404,95%CI:1.074-1.836;allele model:OR=1.273,95%CI:1.034-1.565;homozygous model:OR=1.553,95%CI:1.044-2.310;heterozygous model:OR=1.308,95%CI:1.062-1.611).Conclusion:CTLA-4+49 A/G polymorphism were not associated with the risk of lung cancer but might be a risk factor only in NSCLC.展开更多
基金Supported by the National Natural Science Foundation of China(31301935)Ph.D.Programs Foundation of Ministry of Education of China(20112325120013)
文摘Reproduction trait plays an important role in pig production. Identification of molecular markers that are linked to litter size may contribute to the genetic development of porcine reproduction traits. In this study, porcine ring finger protein 4 （pRNF4） and Matrix metalloproteinase 9 （pMMP-9） were selected as candidate genes on the basis of their physiological roles in reproduction. Two single-nucleotide polymorphisms （416C〉T in pRNF4 and - 1257G〉A in pMMP-9） that could be detected by PCR restriction fragment length polymorphism （PCR-RFLP） were discovered and tested for statistical associations with litter size traits in three populations. For 416C〉T, TT genotype was associated with a significantly higher （p〈0.05） number of live births than those recorded for CC sows and the additive effect was significant （p〈0.05） in Qingping and Min Pigs populations in later parities. For -1257G〉A, inconsistent results were found in three populations. The results suggested that T allele in pRNF4 gene might confer a high prolificacy in breeding and further studies were needed to confLrm the results.
文摘The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan,oxidized by CYP3A4 to produce inactive compounds,is used for treatment of various cancers including advanced non small cell lung cancer (NSCLC) patients. CYP3A4*16B polymorphism was associated with decreased metabolism of irrinotecan. Irinotecan is also metabolized by carboxylesterase to its principal active metabolite,SN-38,which is subsequently glucuronidated by UGT1As to form the inactive compound SN-38G. UGT1A1*28 and UGT1A1*6 polymorphisms were useful for predicting severe toxicity with NSCLC patients treated with irinotecan-based chemotherapy. Platinum-based compounds (cisplatin,carboplatin) are being used in combination with new cytotoxic drugs such as gemcitabine,paclitaxel,docetaxel,or vinorelbine in the treatment of advanced NSCLC. Cisplatin activity is mediated through the formation of cisplatin-DNA adducts. Gene polymorphisms of DNA repair factors are therefore obvious candidates for determinants of repair capacity and chemotherapy efficacy. ERCC1,XRCC1 and XRCC3 gene polymorphisms were a useful marker for predicting better survival in advanced NSCLC patients treated with platinum-based chemotherapy. XPA and XPD polymorphisms significantly increased response to platinum-based chemotherapy. These DNA repair gene polymorphisms were useful as a predictor of clinical outcome to the platinum-based chemotherapy. EGFR kinase inhibitors induce dramatic clinical responses in NSCLC patients with advanced disease. EGFR gene polymorphism in intron 1 contains a polymorphic single sequence dinucleotide repeat (CA-SSR) showed a statistically significant correlation with the gefitinib response and was appeared to be a useful predictive marker of the development of clinical outcome containing skin rashes with gefitinib treatment. The other polymorphisms of EGFR were also associated with increased EGFR promoter activity. EGFR gene mutations and polymorphisms were also associated with EGFR kinase inhibitors response and toxicity.
基金The project supported by National Naural Science Foundation of China(81422052)Special Topic of the Major Subject of National Science and Technology(2012ZX09509-107)Hunan Provincial Natural Science Foundation of China(13JJ1010)
文摘OBJECTIVE To evaluate the association between DNA(cytosine-5)-methyltransferase 3 alpha(DNMT3A)genetic polymorphisms and the disease prognosis of R882 mutation negative acute myeloid leukemia(AML)patients.METHODS DNMT3A 11 SNPs(rs11695471,rs2289195,rs734693,rs2276598,rs1465825,rs7590760,rs13401241,rs7581217,rs749131,rs41284843 and rs7560488)were genotyped using a MassA RRAY platform or Sanger sequencing method in 317 diagnostic non-FABM3 AML patients without R882 mutation from southern China.AML patients underwent combined chemotherapy with cytarabine and anthracyclines.Overall survival(OS)and Disease-free survival(DFS)as major end points were defined.The prognostic(median OS and DFS)evaluations were performed by Kaplan-Meier curve and Cox′s proportional hazard model.RESULTS We found that the rs2289195 G>A SNP could act as a poor prognostic predictor independently(HR=0.442,P=0.035 for OS;HR=0.431,P=0.031 for DFS),while the rs1465825 T>C SNP and rs7590760 G>C SNP appeared to predict independently poor prognosis for both OS(HR=1.453,P=0.037 for rs1465825;HR=1.584,P=0.063 for rs7590760)and DFS(HR=1.459,P=0.057 for rs1465825;HR=1.965,P=0.017for rs7590760).However,no significant associations between other DNMT3A polymorphisms and prognosis(OS in conjunction with DFS)were observed.CONCLUSION DNMT3A polymorphisms may be potential predictive markers for AML prognosis in R882 mutation negative patients,which might improve prognostic stratification of AML.
基金Key Items of Plan of Science and Technology of Heilongjiang Province (CGB01B104)
文摘In order to further study functions of the porcine myostatin gene, we analyzed the polymorphisms of porcine myostatin gene in promoter region among different breeds including Yorkshire, Landrace, Duroc, Junmu, Min pig and Sanjiang white pig by PCR-RFLPs. The allele T dominated in the imported lean-type pig breeds such as Yorkshire, Landrace and Duroc. No allele A was detected in Junmu and Sanjiang white pig, and the frequencies of three genotypes were about equal in Min pig. The result using X2 analysis showed that the distribution of three genotypes was related to pig breeds.
基金Supported by National Natural Sciences Foundation of China(39970533)
文摘Three breeds of sows were observed to investigate the relationship between Single Nucleotide Polymorphisms（SNPs） in Mu Opioid Receptor（MOR）and stereotypic behaviour,such as,sham-chewing,bar biting and standing still in order to better understand the mechanism of stereotypic development of the animals in restrained conditions.MOR exon 2 partial sequences were amplified to analyze single nucleotide polymorphisms by PCR-SSCP.One SNP,a silence mutant was found.A significant difference （P〈0.01）was found in the frequency of genotypes in these 3 breeds where only the BB genotype,which was identical to that published in GenBank,was found in the Duroc breed,while no AA genotype was found in Landrace,3 genotypes AA,BB and AB were found in Yorkshire.The result also indicated that the individuals with AA and AB genotypes tended to be more active in sham-chewing than those with the BB genotype（P〈0.05）.The overall results of this study suggested that sham-chewing of sows may be subjected to both genetic control and environmental conditions,but activity level was more likely to be affected by their environment.We can putatively draw the conclusion that MOR gene has effect on the sham-chewing behavioral traits of sow.
基金Acknowledgments The current research was supported by the Na- tional Natural Science Foundation of China （81302622）, the Science Technology Foundation of Lanzhou （2012-1-22）, and Youth Science and Tech- nology Foundation of Gansu （1208RYYA073）.
文摘The short tandem repeat (STR) markers are widely used in human identification and paternity testing in the field of forensic genetics[1].Recent researches on polymorphic STRs have led to their applications to population genetics,forensic DNA database,human individual identification,paternity testing,genetic mapping,disease linkage analysis,archaeology and potential inference of the ethnic origin of an individual[2].
文摘The cytochrome P450 2El （ CYP2E1 ） and aldehyde dehydrogenase 2 （ALDH2） have been demonstrated that they were related to the development of hepatocellular carcinoma （HCC）. However, the associations have not been explained conclusively, and the combined analysis with the CYP2E1 Rsa I polymorphism and the ALDH2 pol- ymorphism have not been clarifed. In this study, we performed a meta-analysis to interpret the association between CYP2E1 and ALDH2 polymorphisms and HCC risk. Published literatures were retrieved from PubMed and Embase up to July, 2014. The pooled odds ratio （OR） with 95% confidence interval （CI） was calculated by using fixed- effects or random-effects model. A total of twelve case-controlled studies with 1 077 cancer cases and 2 000 controls concerning the CYP2E1 polymorphism were selected for this meta-analysis. The results indicated that there was no significantly associations between CYP2E1 polymorphism and risk of HCC （cl/c2 vs el/el ： OR - 1.11, 95% CI： 0.88-=1.39, P-0.38; c2/c2 vs el/el. OR -0.90, 95% CI. 0.54-=1.50, P-0.69; cl/c2 ＋ c2/c2 vs el/ el ： OR - 1.07, 95% CI： 0.89 -~ 1.30, P -0.47）. Further analysis of subgroup based on the ethnicity also showed no statistically significant associated with risk of HCC between the East Asians and the Europeans. In addi- tion, eight studies including 911 cases and 1 903 controls were included in this meta-analysis about the association between ALDH2 polymorphism and HCC risk. Results Based on our study also showed no significant association between ALDH2 polymorphism and the risk of HCC risk （ ＊ 1/＊ 2 vs ＊ 1/＊ 1： OR -0. 92, 95% CI： 0.65 -＊ 1.32, P-0.66; ,2/,2 vs ＊ 1/＊ 1. OR -0.82, 95% CI. 0.57-=1.18, P-0.28, ＊ 1/,2 ＋ ,2/,2 vs ＊ 1/＊ 1 ： OR -0.90, 95% CI. 0. 63 -- 1.29, P -0. 57）. The present meta-analysis indicated that there was no sig- nificant association between CYP2E1 polymorphism or ALDH2 polymorphism and HCC risk in the East Asians and the Europeans.
文摘OBJECTIVE The purpose of the present study was to investigate the impact of fluvas.tatin formulation on the pharmacokinetics-genetic polymorphis relationship.METHODS We compared the difference between the pharmacokinetics of fluvastatin as an extended-release(ER) 80 mg tablet and an immediate-release(IR) 40 mg capsule in terms of drug metabolism enzyme and transporter ge.netic polymorphisms.In this open-label,randomized,two-period,two-treatment,crossover study,ef.fects of BCRP,SLCO1B1,MDR1,CYP2C9,and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed in 24 healthy individuals.Each treatment duration was 7 days with a washout period of 7 days between the crossover.Serum concentration of fluvastatin was evaluated using highperformance liquid chromatography-tandem mass spectrometry.RESULTS The SLCO1 B1 T521 C genotype had no statistically significant effect on IR 40 mg capsule of fluvastatinafter single or repeated doses.However,for the ER 80 mg tablet,the SLCO1 B1 T521 C genotype correlated with the AUC_(0-24) of repeat doses(P=0.01).The CYP2C9*3 genotype correlated with the AUC_(0-24) after the first dose IR40 mg capsule(P<0.05);however,the difference between CYP2C9*1/*1 and CYP2 C9*1/*3 was not statistically significant after repeated doses.CONCLUSION The effect of SLCO1B1T521C on fluvas.tatin exposure was observed and was more profound in ER and repeated dose administration than in IR and single dose administration.We recommend that formulation should be incorporated into future pharmacogenomics studies and clinical implication guidelines.
文摘The BRCA1 Associated RING Domain(BARD1) gene has been identified as a high penetrance gene for breast cancer, whose germline and somatic mutations were reported in both non-BRCA1/2 hereditary site-specific and sporadic breast cancer cases. BARD1 plays a crucial role in tumor repression, along with its heterodimeric partner BRCA1. In the current study, we tested the hypothesis that common non-synonymous polymorphisms in BARD1 are associated with breast cancer susceptibility in a case-control study of 507 patients with incident breast cancer and 539 frequency-matched cancer-free controls in Chinese women. We genotyped all three common(minor allele frequency (MAF) > 0.10) non-synonymous polymorphisms(Pro24Ser, Arg378Ser, and Val507Met) in BARD1. We found that the BARD1 Pro24Ser variant genotypes(24Pro/Ser and 24Ser/Ser) and Arg378Ser variant homozygote 378Ser/Ser were associated with a significantly decreased breast cancer risk, compared with their wild-type homozygotes, respectively. Furthermore, a significant locus-locus interaction was evident between Pro24Ser and Arg378Ser (P-int = 0.032). Among the 378Ser variant allele carriers, the 24Pro/Pro wild-type homozygote was associated with a significantly increased breast cancer risk (adjusted OR = 1.81, 95% CI = 1.11-2.95), but the subjects having 24Pro/Ser or Ser/Ser variant genotypes had a significantly decreased risk(adjusted OR = 0.74, 95% CI = 0.56-0.99). In stratified analysis, this locus-locus interaction was more evident among subjects without family cancer history, those with positive estrogen receptor (ER) and individuals with negative progesterone receptor(PR). These findings indicate that the potentially functional polymorphisms Pro24Ser and Arg378Ser in BARD1 may jointly contribute to the susceptibility of breast cancer.
基金This project was carried out under the financial support of USM short-term grant(304/PPSP/6131324)
文摘Aim:In this study,we would like to determine associations between β2-Adrenergic Receptor(β2AR)polymorphisms at codon 16 and 27 and the response to short acting β2-agonist during asthmatic exacerbation.Methods:This was a prospective cross-sectional study of one year duration.One hundred and thirty two asthmatic patients were recruited.Five mls of venous blood was taken for DNA extraction and then genotyped for the β2AR polymorphisms using multiplex PCR.Patient's clinical responses to β2-agonist nebulization were then compared to their genotype to determine the association.Results:We found that there was no association between β2AR polymorphisms at both codon 16 and 27 with response towards short acting β2-agonist,P=0.315 and P=0.706 respectively.Conclusion:We suggested that β2AR polymorphisms at both codon 16 and 27 had no influent on the response to short acting β2-agonist.
基金support for this study by the National Natural Science Foundation of China(Grant No.22275175)。
文摘Herein,a first example of energetic-energetic cocrystal polymorphs with a 1:1 M ratio was discovered by cocrystallizing CL-20(2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane)with 1,3-DNP(1,3-dinitropyrazole).These two energetic cocrystal polymorphs(cocrystal 1 and cocrystal 2)exhibit distinct crystal packing styles,which lead to significant variations in their physicochemical properties.Notably,cocrystal 2 has a high density of 1.963 g·cm^(-3)at 170 K,exhibiting high detonation performances(9187 m·s^(-1);38.68 GPa)comparable to HMX(1,3,5,7-tetranitro-1,3,5,7-tetrazocane)meanwhile displaying an improved safety(10 J)relative to RDX(1,3,5-trinitro-1,3,5-triazinane),making it a potential high-energy,low-sensitivity energetic material.This work opens up a new strategy to deeply tune properties of energetic materials by constructing energetic-energetic cocrystal polymorphs.These energetic cocrystal polymorphs represent a new field of energetic materials that has not yet been studied.
基金financial support of this work by Malek-ashtar University of Technology(I.R.Iran)Grant No.1395064
文摘A seeding strategy was developed in the preparation of cyclotetramethylenetetranitramine(HMX)explosive micro-particles by solvent-antisolvent method, to control their polymorphs from dangerous gamma(y) type to the desired and standard beta(β) form with the size distribution of <10.0 μm, by using a low concentration of β-HMX fine particles as micro-seed in the antisolvent medium. All products were characterized by X-ray diffraction(XRD), scanning electron microscopy(SEM), and dynamic light scattering particle size analyzer. In the next step, the effective factors on the sizes and morphologies of micro-particles in the presence and absence of two soft templates of poly(ethylene glycol)-400(PEG-400) polymer and coconut fatty acid diethanolamide(lauramide) surfactant were investigated. The results of experiments showed that using of water-soluble PEG-400 in the low antisolvent temperatures leads to the production of very spherical particles. Also non-ionic surfactant of lauramide, direct the crystal growth to needle-like structures. The advantages of this method are its capability for the simple production of β-HMX micro-particles in the large scale production process, with the various crystal structures and particles size distributions.
基金Supported by National Key Technology R&D Program in the 11th Five Year Plan of China (2008BADB2B01)
文摘The follicle stimulating hormone beta-subunit （FSHβ） gene plays an important role in piglets. Marker-assisted selection （MAS） in conjunction with traditional selection methods is most effective for improving the piglets breeding traits. To find the new SNPs, the polymorphism of it in six pig breeds （Min, Landrace, Yorkshine, Duroc, wild boar, and wild boar × Landrace） was analyzed by using PCR-SSCP and was further compared with each other. Polymorphism was found and the sequencing results showed that there was one silent mutation on exon2 （C48T） and two mutations on exon3 （T422C and A514G）. Genotype distribution of FSHβ in Min and wild boar on exon3 was in accordance with Hardy-Weinberg Law.
基金Supported by Program for New Century Excellent Talents in University(NCET-04-0343)National Natural Science Foundation Key Project(30430510)Excellent Young Teachers Program of MOE.People's Republic of China(1985)
文摘Based on chicken＇ consensus map issued in 2000, 17 microsatellites near 4 candidate genes such as IGF2, OBR, GDF8 and APOA 1 in 4 chromosomes （chromosome 5, 7, 8 and 24） were chosen for polymorphism analysis and construction of linkage map. Combining the technique of PCR and the fluorescent semi-automated detection, genome scanning was performed for 440 chickens, which was derived from China Agricultural University chicken resource families within three generations. The individuals of this resource families were genotyped. The results showed that the number of alleles ranged from 4 to 14; heterozygosity （H） of markers was between 0.3116 and 0.9148. Polymorphic information content （PIC） varied from 0.2672 to 0.8679. Microsatellites along with above-mentioned 4 candidate genes doing as general markers were used to construct linkage map. The spans of 4 linkage maps constructed in the part region of chromosome 5, 7, 8 and 24 were 263.5, 79.9, 206.2 and 104.2 cM, respectively. The order of markers was consistent with that of counterpart of reported consensus map. However, The spans of linkage map were larger than that of consensus map. The constructed linkage maps laid the foundation for mapping quantitative trait loci （QTL） responsible for economically important traits in chicken.
文摘Background and objective:Lung cancer is one of the malignant tumors.Gene mutations associated with cellular immune function and regulating the activation and proliferation of immune cells.Several publications have explored the relationship between cytotoxic T lymphocyte antigen-4(CTLA-4)+49 adenine(A)/guanine(G)polymorphism and susceptibility of lung cancer,but the results remain controversial.Thus,we performed this meta-analysis to derive a more comprehensive estimation of the relationship.Methods:All articles addressed lung cancer and polymorphisms of CTLA-4 were searched from the Pub Med,EMBASE databases published up to June 29,2019.Odds ratios(ORs)with 95%confidence intervals(CIs)were used to assess the strength of association.Publication bias of relevant studies was examined via Begg’s test and funnel plots.Results:The meta-analysis included 8 case-control studies covering 4,430 lung cancer patients and 5,198 healthy controls from September 2008 to April 2020.The overall eligible data indicated that CTLA-4+49 A/G polymorphisms did not correlate with the elevated lung cancer risk in all genetic comparison models(dominant model:OR=1.037,95%CI:0.925-1.161;recessive model:OR=0.968,95%CI:0.888-1.055;allele model:OR=0.992,95%CI:0.933-1.054;homozygous model:OR=0.980,95%CI:0.857-1.121;heterozygous model:OR=1.023,95%CI:0.906-1.154).In further stratified analyses,CTLA-4+49 A/G polymorphism was found to be significantly associated with susceptibility to NSCLC in these models(dominant model:OR=1.404,95%CI:1.074-1.836;allele model:OR=1.273,95%CI:1.034-1.565;homozygous model:OR=1.553,95%CI:1.044-2.310;heterozygous model:OR=1.308,95%CI:1.062-1.611).Conclusion:CTLA-4+49 A/G polymorphism were not associated with the risk of lung cancer but might be a risk factor only in NSCLC.
