With completion of the Populus genome sequencing project and the availability of many expressed sequence tags （ESTs） databases in forest trees, attention is now rapidly shifting towards the study of individual genet...With completion of the Populus genome sequencing project and the availability of many expressed sequence tags （ESTs） databases in forest trees, attention is now rapidly shifting towards the study of individual genetic variation in natural populations. The most abundant form of genetic variation in many eukaryotic species is represented by single nucleotide polymorphisms （SNPs）, which can account for heritable inter-individual differences in complex phenotypes. Unlike humans, the linkage disequilibrium （LD） rapidly decays within candidate genes in forest trees. Thus, SNPs-based candidate gene association studies are considered to be a most effective approach to dissect the complex quantitative traits in forest trees. The present study demonstrates that LD mapping can be used to identify alleles associated with quantitative traits and suggests that this new approach could be particularly useful for performing breeding programs in forest trees. In this review, we will describe the fundamentals, patterns of SNPs distribution and frequency, summarize recent advances in SNPs discovery and LD and comment on the application of LD in the dissection of complex quantitative traits in forest tress. We also put forward the outlook for future SNPs-based association analysis of quantitative traits in forest trees.展开更多
Nucleotide diversity (pi) and linkage disequilibrium (LD) analysis based on SNP marker could provide a sound basis for choosing an association analysis method. Japanese larch (Larix kaempferi) is an important timber c...Nucleotide diversity (pi) and linkage disequilibrium (LD) analysis based on SNP marker could provide a sound basis for choosing an association analysis method. Japanese larch (Larix kaempferi) is an important timber coniferous tree species for pulping and papermaking, but its high lignin content has significantly restricted it application potential. In this study, the LACCASE gene, that plays an important regulatory role for lignin biosynthesis, was selected as research target. The full-length cDNA and genomic sequences of the encoding LkLAC8 gene were isolated from the LACCASE expressed sequence tags of the Japanese larch transcriptome database using the rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR). The cDNA was determined to be 1940 bp, with an open reading frame (ORF, 1734 bp) that encoded a protein of 577 AA. This protein contains four highly specific Cu2+ binding sites and 11 glycosylation sites, thus belonging to the LACCASE family. The deduced protein sequence shared an 89% identity with the PtaLAC from Pinus taeda. A real-time PCR analysis showed that the LkLAC8 transcript was expressed predominantly in mature xylem, with moderate levels in the immature xylem, cambium and mature leaves, the lowest in the roots. Lastly, the genomic sequences of LkLAC8 in 40 individuals from six naturally distributed populations of Japanese larch were amplified, and a total of 201 SNPs (103 and 98 mutation types of transition and transversion, respectively) were detected; the frequency of the SNPs was 1/19 bp. Nucleotide diversity among the six populations ranged from 0.0034 to 0.0053, which suggested that there were no significant differences among the populations. The LD analysis showed that the LD level decayed rapidly within the increasing length of the LkLAC8 gene. These results implied that LD mapping and association analysis based on candidate gene may be feasible for the marker-assisted breeding of new germplasms with low lignin in Japanese larch.展开更多
Objectives To study the association of single nucleotide polymorphism （SNP） rs2076185 in chromosome 6p24.1 with the premature coronary artery diseases （PCAD） in Chinese Hun population. Methods A total of 1382 pati...Objectives To study the association of single nucleotide polymorphism （SNP） rs2076185 in chromosome 6p24.1 with the premature coronary artery diseases （PCAD） in Chinese Hun population. Methods A total of 1382 patients were divided into the PCAD group and the control group based on their coronary arteriography （CAG） results. Their SNP rs2076185 were analyzed by the mass-spectrometry. Their allele and genotype frequency in Hardy-Weinberg equilibrium were calculated for assessment. Logistic regression was employed to remove confounding factors and correlate SNP rs2076185 with PCAD. Results The allele and genotype frequencies of the control group were in Hardy-Weinberg equilibrium （P 〉 0.05）. The frequencies of allele G of rs2076185 were 54.2% in the PCAD group and 49.5% in the control group. The difference was significant （P = 0.042）. The genotype distribution ofrs2076185 of the two groups was also significantly different. The univariate analysis showed that the rs2076185 polymorphisms were associated with the PCAD only in the additive model （OR： 0.828, 95% CI： 0.711-0.964, P = 0.014）, and in the dominant model （OR： 0.753, 95% CI： 0.591-0.958, P = 0.021）. After removing the confound- ing variables, the rs2076185 polymorphisms was associated with PCAD in the additive model （OR： 0.775, 95% CI： 0.648-0.928, P = 0.005）, in the dominant model （OR： 0.698, 95% CI： 0.527-0.925, P = 0.012）, and in the recessive model （OR： 0.804, 95% CI： 0.538-0.983, P - 0.038）. Conclusion Allele G of rs2076185 reduces the PCAD risks in Chinese Hun population, therefore it could be a coronary artery diseases protective factor in Chinese Hun population.展开更多
Objective: To establish a novel approach for quick and highly efficient verification of human gene imprinting. Methods: A pair of dye-labelled probes, 5' nuclease assay was combined with RT-PCR to determine the ge...Objective: To establish a novel approach for quick and highly efficient verification of human gene imprinting. Methods: A pair of dye-labelled probes, 5' nuclease assay was combined with RT-PCR to determine the genotype of a transcribed single nucleotide polymorphism (SNP) rs705(C>T) of a known imprinted gene, small nuclear ribonucleotide protein N (SNRPN), on both genomic DNA and cDNA of human lym-phoblast cell lines. Results: Allele discrimination showed a clear monoallelic expression pattern of SNRPN, which was confirmed by RT-PCR based restriction fragment length polymorphism (RFLPs). Pedigree analysis verified the paternal origin of expressed allele, which was in consistency with previous report. Conclusion: Transcribed SNP is an ideal marker for detecting gene imprinting by 5' nuclease assay. This approach also may be used to discover differential allele expression of non-imprinted genes, finding out gene cis-acting functional polymorphism.展开更多
Single nucleotide polymorphisms （SNP） of ATP-binding cassette transporter A1 （ABCA1） gene are related to plasma lipid and susceptibility to coronary artery disease （CAD）. Our first goal was to screen all 50 codi...Single nucleotide polymorphisms （SNP） of ATP-binding cassette transporter A1 （ABCA1） gene are related to plasma lipid and susceptibility to coronary artery disease （CAD）. Our first goal was to screen all 50 coding regions of ABCA1 to find new SNPs. Our second goal was to investigate the frequency distribution of R1587K and M883I polymorphisms of ABCA1 gene, which are the variant occurred most frequently, in Chinese people and to evaluate their association with the CAD phenotype and plasma lipids. Methods： Single-strand conformation polymorphism （SSCP） and DNA sequence were used for confirming new SNP of ABCA1, and restriction fragment length polymorphism （RFLP） were applied for confirming genotypes of R1587K and M883I in 112 CAD cases and 108 healthy people. Results： We discovered a new ABCA1 SNP in Chinese population, which converse 233 amino acids from Methionine to Valine （M233V）. This new ABCA1 SNP located in exon7, and might potentially modulate the biological function of lipid metabolism. For R1587K and M883I SNPs, the K allele and I allele frequency was 28.9% and 31.1%, respectively. The K allele at R1587K conferred lower mean values of HDL-C in a dose-dependent manner in both CAD patients and healthy people. However, 883I allele was not associated with plasma lipid level. Neither 1587KK nor 883II associated with increased risk of CAD. Conclusion： Our study finds a potential functional ABCA1 SNPs and revealed K allele of R1587K associated decreased HDL-C level in Chinese population.展开更多
Objective To identify the possible association between C（-106）T polymorphism of the aldose reductase （ALR） gene and diabetic retinopathy （DR） in a cohort of Chinese patients with type 2 diabetes mellitus （T2DM...Objective To identify the possible association between C（-106）T polymorphism of the aldose reductase （ALR） gene and diabetic retinopathy （DR） in a cohort of Chinese patients with type 2 diabetes mellitus （T2DM）. Methods From November 2009 to September 2010, patients with T2DM were recruited and assigned to DR group or diabetic without retinopathy （DWR） group according to the duration of diabetes and the grading of 7-field fundus color photographs of both eyes. Genotypes of the C（-106）T polymorphism （rs759853） in ALR gene were analyzed using the MassARRAY genotyping system and an association study was performed. Results A total of 268 T2DM patients （129 in the DR group and 139 in the DWR group） were included in this study. No statistically significant differences were observed between the 2 groups in the age of diabetes onset （P=0.10） and gender （P=0.78）. The success rate of genotyping for the study subjects was 99.6% （267/268）, with one case of failure in the DR group. The frequencies of the T allele in the C（-106）T polymorphism were 16.0% （41/256） in the DR group and 19.4% （54/278） in the DWR group （P=0.36）. There was no signit^cant difference in the C（-106）T genotypes between the 2 groups （P=0.40）. Compared with the wild-type genotype, odds ratio （OR） for the risk of DR was 0.7 （95% CI, 0.38-1.3） for the heterozygous CT genotype and 0.76 （95% CI, 0.18-3.25） for the homozygous TT genotype. The risk of DR was positively associated with microalbuminuria （OR=4.61; 95% CI, 2.34-9.05） and insulin therapy （OR=3.43; 95% CI, 1.94-6.09）. Conclusions Microalbuminuria and insulin therapy are associated with the risk of DR in Chinese patients with T2DM. C（-106）T polymorphism of the ALR gene may not be significantly associated with DR in Chinese patients with T2DM.展开更多
BACKGROUND: Triggering receptor expressed on myeloid cells-1(TREM-1) is a cell surface receptor expressed on neutrophils and monocytes. TREM-1 acts to amplify infl ammation and serves as a critical mediator of infl am...BACKGROUND: Triggering receptor expressed on myeloid cells-1(TREM-1) is a cell surface receptor expressed on neutrophils and monocytes. TREM-1 acts to amplify infl ammation and serves as a critical mediator of infl ammatory response in the context of sepsis. To date, the predisposition of TREM-1 gene polymorphisms to septic shock has not been reported. This study was designed to investigate whether TREM-1 genomic variations are associated with the development of septic shock.METHODS: We genotyped two TREM-1 single nucleotide polymorphisms(SNPs, rs2234237 and rs2234246) and evaluated the relationships between these SNPs and septic shock on susceptibility and prognosis.RESULTS: TREM-1 rs2234246 A allele in the promoter region was signifi cantly associated with the susceptibility of septic shock in recessive model(AA, OR=3.10, 95%CI 1.15 to 8.32, P=0.02), and in codominant model(AG, OR=0.72, 95%CI 0.43–1.19, P=0.02; AA, OR=2.71, 95%CI 1.00–7.42; P=0.03). However, in three inherited models(dominant model, recessive model, and codominant model), none of the assayed loci was signif icantly associated with the prognosis of septic shock. The nonsurvivor group demonstrated higher plasma IL-6 levels(99.7±34.7 pg/mL vs. 61.2±26.5 pg/mL, P<0.01) than the survivor group. Plasma concentrations of IL-6 among the three genotypes of rs2234246 were AA 99.4±48.9 pg/m L, AG 85.4±43 pg/m L, and GG 65.3±30.7 pg/m L(P<0.01). The plasma concentrations of IL-6 in patients with AA genotypes were signifi cantly higher than those in patients with GG genotypes(P<0.01).CONCLUSION: TREM-1 genetic polymorphisms rs2234246 may be significantly correlated only with susceptibility to septic shock in the Chinese Han population.展开更多
Objective To investigate the relationship between geranylgeranyl pyrophosphate synthase （GGPPS） gene polymorphisms and bone response to alendronate in Chinese osteoporotic women. Methods A total of 639 postmenopaus...Objective To investigate the relationship between geranylgeranyl pyrophosphate synthase （GGPPS） gene polymorphisms and bone response to alendronate in Chinese osteoporotic women. Methods A total of 639 postmenopausal women with osteoporosis or osteopenia were included and randomly received treatment of low dose （70 mg per two weeks） or standard dose （70 mg weekly） of alendronate for one year. The six tag single nucleotide polymorphisms of GGPPS gene were identified. Bone mineral density （BMD）, serum cross-linked C-telopeptide of type I collagen （β-CTX）, and total alkaline phosphatase （ALP） were measured before and after treatment. GGPPS gene polymorphisms and the changes of BMD and bone turnover markers after treatment were analyzed. Results rs10925503 polymorphism of GGPPS gene was correlated to serumβ-CTX levels at baseline, and patients with TT genotype had significantly higher serum β-CTX level than those with TC or CC genotype （all P〈0.05）. No correlation was found between polymorphisms of GGPPS gene and serum total ALP levels, as well as BMD at baseline. After 12 months of treatment, lumbar spine and hip BMD increased and serum bone turnover markers decreased significantly （P〈0.01）, and without obvious differences between the low dose and standard dose groups （all P〉0.05）. However, GGPPS gene polymorphisms were uncorrelated to percentage changes of BMD, serum total ALP, and β-CTX levels （all P〉0.05）. Conclusion GGPPS gene polymorphisms are correlated to osteoclasts activity, but all tag single nucleotide polymorphisms of GGPPS gene have no influence on the skeletal response to alendronate treatment.展开更多
Objective: Peroxisome proliferator-activated receptor -γ(PPAR-γ) plays a critical role in adipocyte differentiation and the development of type 2 diabetes mellitus (T2DM). Numerous studies across several populations...Objective: Peroxisome proliferator-activated receptor -γ(PPAR-γ) plays a critical role in adipocyte differentiation and the development of type 2 diabetes mellitus (T2DM). Numerous studies across several populations have indicated that Pro12Ala polymorphism of PPAR-γ is associated with decreased insulin resistance and decreased risk of T2DM. The aims of this study are to develop a simple and sensitive detection of Pro12Ala polymorphism and examined the distribution of this polymorphism in Chinese population. Methods: The PPAR-γ gene fragment containing Pro12Ala variant of 101 T2DM patients and 104 controls were amplified by PCR amplification and the extension reaction was performed using primer that adjacent to the single nucleotide polymorphic site in presence of two different dye-labeled terminators. The primer's specially extending reactions make the increase of their fluorescence polarization (FP) that mean special genotype. The variant frequencies of the two groups were compared. Results: We detected the Pro12Ala variant successfully by TDI-FP method and we found no significant association between this polymorphism and T2DM in case-control study. Conclusion: The TDI-FP technology is a new specific and sensitive method that is suitable for automatic detection of large number of clinical samples. Prol2Ala mutation in PPAR--@2 gene does not play a significant role in T2DM risk in Chinese population.展开更多
Atrial fibrillation (AF) is the most common arrhythmia with multi-factorial pathogenesis. A number of studies of genetic epidemiology have assessed the association of G112A (G38S) single nucleotide polymorphisms (SNPs...Atrial fibrillation (AF) is the most common arrhythmia with multi-factorial pathogenesis. A number of studies of genetic epidemiology have assessed the association of G112A (G38S) single nucleotide polymorphisms (SNPs) in Mink gene with AF in different populations. However, the results are inconsistent and inconclusive. We performed a Meta-analysis of the association between G112A polymorphisms of MinK gene and AF to estimate the magnitude of the gene effect. Six case-control studies with a combined 854 cases and 1079 controls were summarized. Subgroups in different races were separately analyzed. Heterogeneity and publication bias were also explored. When all groups were pooled, the individuals with G allele had an over 40% higher risk of AF compared with individuals with the A allele. The GG genotype (versus AA genotype) was found to be significant association with increased AF risk. The significant associations were also found in both dominant and recessive genetic model. For subgroup analysis, the results were consistent with above, except that the pooled OR for Chinese population was not significant in a recessive genetic model. In conclusion, G112A polymorphisms in Mink gene may have an important effect on the pathogenesis of AF. This warrants further investigation in large multi-center studies with precise design.展开更多
文摘With completion of the Populus genome sequencing project and the availability of many expressed sequence tags （ESTs） databases in forest trees, attention is now rapidly shifting towards the study of individual genetic variation in natural populations. The most abundant form of genetic variation in many eukaryotic species is represented by single nucleotide polymorphisms （SNPs）, which can account for heritable inter-individual differences in complex phenotypes. Unlike humans, the linkage disequilibrium （LD） rapidly decays within candidate genes in forest trees. Thus, SNPs-based candidate gene association studies are considered to be a most effective approach to dissect the complex quantitative traits in forest trees. The present study demonstrates that LD mapping can be used to identify alleles associated with quantitative traits and suggests that this new approach could be particularly useful for performing breeding programs in forest trees. In this review, we will describe the fundamentals, patterns of SNPs distribution and frequency, summarize recent advances in SNPs discovery and LD and comment on the application of LD in the dissection of complex quantitative traits in forest tress. We also put forward the outlook for future SNPs-based association analysis of quantitative traits in forest trees.
基金financially supported by the Fundamental Research Funds for the Central Non-profit Research Institution of CAF(RIF2014-06)the Forestry Industry Research special funds for Public Welfare Projects(201504104)
文摘Nucleotide diversity (pi) and linkage disequilibrium (LD) analysis based on SNP marker could provide a sound basis for choosing an association analysis method. Japanese larch (Larix kaempferi) is an important timber coniferous tree species for pulping and papermaking, but its high lignin content has significantly restricted it application potential. In this study, the LACCASE gene, that plays an important regulatory role for lignin biosynthesis, was selected as research target. The full-length cDNA and genomic sequences of the encoding LkLAC8 gene were isolated from the LACCASE expressed sequence tags of the Japanese larch transcriptome database using the rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR). The cDNA was determined to be 1940 bp, with an open reading frame (ORF, 1734 bp) that encoded a protein of 577 AA. This protein contains four highly specific Cu2+ binding sites and 11 glycosylation sites, thus belonging to the LACCASE family. The deduced protein sequence shared an 89% identity with the PtaLAC from Pinus taeda. A real-time PCR analysis showed that the LkLAC8 transcript was expressed predominantly in mature xylem, with moderate levels in the immature xylem, cambium and mature leaves, the lowest in the roots. Lastly, the genomic sequences of LkLAC8 in 40 individuals from six naturally distributed populations of Japanese larch were amplified, and a total of 201 SNPs (103 and 98 mutation types of transition and transversion, respectively) were detected; the frequency of the SNPs was 1/19 bp. Nucleotide diversity among the six populations ranged from 0.0034 to 0.0053, which suggested that there were no significant differences among the populations. The LD analysis showed that the LD level decayed rapidly within the increasing length of the LkLAC8 gene. These results implied that LD mapping and association analysis based on candidate gene may be feasible for the marker-assisted breeding of new germplasms with low lignin in Japanese larch.
文摘Objectives To study the association of single nucleotide polymorphism （SNP） rs2076185 in chromosome 6p24.1 with the premature coronary artery diseases （PCAD） in Chinese Hun population. Methods A total of 1382 patients were divided into the PCAD group and the control group based on their coronary arteriography （CAG） results. Their SNP rs2076185 were analyzed by the mass-spectrometry. Their allele and genotype frequency in Hardy-Weinberg equilibrium were calculated for assessment. Logistic regression was employed to remove confounding factors and correlate SNP rs2076185 with PCAD. Results The allele and genotype frequencies of the control group were in Hardy-Weinberg equilibrium （P 〉 0.05）. The frequencies of allele G of rs2076185 were 54.2% in the PCAD group and 49.5% in the control group. The difference was significant （P = 0.042）. The genotype distribution ofrs2076185 of the two groups was also significantly different. The univariate analysis showed that the rs2076185 polymorphisms were associated with the PCAD only in the additive model （OR： 0.828, 95% CI： 0.711-0.964, P = 0.014）, and in the dominant model （OR： 0.753, 95% CI： 0.591-0.958, P = 0.021）. After removing the confound- ing variables, the rs2076185 polymorphisms was associated with PCAD in the additive model （OR： 0.775, 95% CI： 0.648-0.928, P = 0.005）, in the dominant model （OR： 0.698, 95% CI： 0.527-0.925, P = 0.012）, and in the recessive model （OR： 0.804, 95% CI： 0.538-0.983, P - 0.038）. Conclusion Allele G of rs2076185 reduces the PCAD risks in Chinese Hun population, therefore it could be a coronary artery diseases protective factor in Chinese Hun population.
文摘Objective: To establish a novel approach for quick and highly efficient verification of human gene imprinting. Methods: A pair of dye-labelled probes, 5' nuclease assay was combined with RT-PCR to determine the genotype of a transcribed single nucleotide polymorphism (SNP) rs705(C>T) of a known imprinted gene, small nuclear ribonucleotide protein N (SNRPN), on both genomic DNA and cDNA of human lym-phoblast cell lines. Results: Allele discrimination showed a clear monoallelic expression pattern of SNRPN, which was confirmed by RT-PCR based restriction fragment length polymorphism (RFLPs). Pedigree analysis verified the paternal origin of expressed allele, which was in consistency with previous report. Conclusion: Transcribed SNP is an ideal marker for detecting gene imprinting by 5' nuclease assay. This approach also may be used to discover differential allele expression of non-imprinted genes, finding out gene cis-acting functional polymorphism.
基金Supported by the Natural Scientific Foundation of China (30471929)
文摘Single nucleotide polymorphisms （SNP） of ATP-binding cassette transporter A1 （ABCA1） gene are related to plasma lipid and susceptibility to coronary artery disease （CAD）. Our first goal was to screen all 50 coding regions of ABCA1 to find new SNPs. Our second goal was to investigate the frequency distribution of R1587K and M883I polymorphisms of ABCA1 gene, which are the variant occurred most frequently, in Chinese people and to evaluate their association with the CAD phenotype and plasma lipids. Methods： Single-strand conformation polymorphism （SSCP） and DNA sequence were used for confirming new SNP of ABCA1, and restriction fragment length polymorphism （RFLP） were applied for confirming genotypes of R1587K and M883I in 112 CAD cases and 108 healthy people. Results： We discovered a new ABCA1 SNP in Chinese population, which converse 233 amino acids from Methionine to Valine （M233V）. This new ABCA1 SNP located in exon7, and might potentially modulate the biological function of lipid metabolism. For R1587K and M883I SNPs, the K allele and I allele frequency was 28.9% and 31.1%, respectively. The K allele at R1587K conferred lower mean values of HDL-C in a dose-dependent manner in both CAD patients and healthy people. However, 883I allele was not associated with plasma lipid level. Neither 1587KK nor 883II associated with increased risk of CAD. Conclusion： Our study finds a potential functional ABCA1 SNPs and revealed K allele of R1587K associated decreased HDL-C level in Chinese population.
基金Supported by the National Basic Research Program of China(973 Program,2007CB512201)the Beijing Municipal Health Bureau Grant(2009208)the Beijing Natural Science Foundation(7131007)
文摘Objective To identify the possible association between C（-106）T polymorphism of the aldose reductase （ALR） gene and diabetic retinopathy （DR） in a cohort of Chinese patients with type 2 diabetes mellitus （T2DM）. Methods From November 2009 to September 2010, patients with T2DM were recruited and assigned to DR group or diabetic without retinopathy （DWR） group according to the duration of diabetes and the grading of 7-field fundus color photographs of both eyes. Genotypes of the C（-106）T polymorphism （rs759853） in ALR gene were analyzed using the MassARRAY genotyping system and an association study was performed. Results A total of 268 T2DM patients （129 in the DR group and 139 in the DWR group） were included in this study. No statistically significant differences were observed between the 2 groups in the age of diabetes onset （P=0.10） and gender （P=0.78）. The success rate of genotyping for the study subjects was 99.6% （267/268）, with one case of failure in the DR group. The frequencies of the T allele in the C（-106）T polymorphism were 16.0% （41/256） in the DR group and 19.4% （54/278） in the DWR group （P=0.36）. There was no signit^cant difference in the C（-106）T genotypes between the 2 groups （P=0.40）. Compared with the wild-type genotype, odds ratio （OR） for the risk of DR was 0.7 （95% CI, 0.38-1.3） for the heterozygous CT genotype and 0.76 （95% CI, 0.18-3.25） for the homozygous TT genotype. The risk of DR was positively associated with microalbuminuria （OR=4.61; 95% CI, 2.34-9.05） and insulin therapy （OR=3.43; 95% CI, 1.94-6.09）. Conclusions Microalbuminuria and insulin therapy are associated with the risk of DR in Chinese patients with T2DM. C（-106）T polymorphism of the ALR gene may not be significantly associated with DR in Chinese patients with T2DM.
基金supported by Science&Technology Pillar Program of Guangdong Province(2009BAI86B03)
文摘BACKGROUND: Triggering receptor expressed on myeloid cells-1(TREM-1) is a cell surface receptor expressed on neutrophils and monocytes. TREM-1 acts to amplify infl ammation and serves as a critical mediator of infl ammatory response in the context of sepsis. To date, the predisposition of TREM-1 gene polymorphisms to septic shock has not been reported. This study was designed to investigate whether TREM-1 genomic variations are associated with the development of septic shock.METHODS: We genotyped two TREM-1 single nucleotide polymorphisms(SNPs, rs2234237 and rs2234246) and evaluated the relationships between these SNPs and septic shock on susceptibility and prognosis.RESULTS: TREM-1 rs2234246 A allele in the promoter region was signifi cantly associated with the susceptibility of septic shock in recessive model(AA, OR=3.10, 95%CI 1.15 to 8.32, P=0.02), and in codominant model(AG, OR=0.72, 95%CI 0.43–1.19, P=0.02; AA, OR=2.71, 95%CI 1.00–7.42; P=0.03). However, in three inherited models(dominant model, recessive model, and codominant model), none of the assayed loci was signif icantly associated with the prognosis of septic shock. The nonsurvivor group demonstrated higher plasma IL-6 levels(99.7±34.7 pg/mL vs. 61.2±26.5 pg/mL, P<0.01) than the survivor group. Plasma concentrations of IL-6 among the three genotypes of rs2234246 were AA 99.4±48.9 pg/m L, AG 85.4±43 pg/m L, and GG 65.3±30.7 pg/m L(P<0.01). The plasma concentrations of IL-6 in patients with AA genotypes were signifi cantly higher than those in patients with GG genotypes(P<0.01).CONCLUSION: TREM-1 genetic polymorphisms rs2234246 may be significantly correlated only with susceptibility to septic shock in the Chinese Han population.
基金Supported by National Natural Science Foundation of China(81570802)National Key Program of Clinical Science(WBYZ2011-873)
文摘Objective To investigate the relationship between geranylgeranyl pyrophosphate synthase （GGPPS） gene polymorphisms and bone response to alendronate in Chinese osteoporotic women. Methods A total of 639 postmenopausal women with osteoporosis or osteopenia were included and randomly received treatment of low dose （70 mg per two weeks） or standard dose （70 mg weekly） of alendronate for one year. The six tag single nucleotide polymorphisms of GGPPS gene were identified. Bone mineral density （BMD）, serum cross-linked C-telopeptide of type I collagen （β-CTX）, and total alkaline phosphatase （ALP） were measured before and after treatment. GGPPS gene polymorphisms and the changes of BMD and bone turnover markers after treatment were analyzed. Results rs10925503 polymorphism of GGPPS gene was correlated to serumβ-CTX levels at baseline, and patients with TT genotype had significantly higher serum β-CTX level than those with TC or CC genotype （all P〈0.05）. No correlation was found between polymorphisms of GGPPS gene and serum total ALP levels, as well as BMD at baseline. After 12 months of treatment, lumbar spine and hip BMD increased and serum bone turnover markers decreased significantly （P〈0.01）, and without obvious differences between the low dose and standard dose groups （all P〉0.05）. However, GGPPS gene polymorphisms were uncorrelated to percentage changes of BMD, serum total ALP, and β-CTX levels （all P〉0.05）. Conclusion GGPPS gene polymorphisms are correlated to osteoclasts activity, but all tag single nucleotide polymorphisms of GGPPS gene have no influence on the skeletal response to alendronate treatment.
文摘Objective: Peroxisome proliferator-activated receptor -γ(PPAR-γ) plays a critical role in adipocyte differentiation and the development of type 2 diabetes mellitus (T2DM). Numerous studies across several populations have indicated that Pro12Ala polymorphism of PPAR-γ is associated with decreased insulin resistance and decreased risk of T2DM. The aims of this study are to develop a simple and sensitive detection of Pro12Ala polymorphism and examined the distribution of this polymorphism in Chinese population. Methods: The PPAR-γ gene fragment containing Pro12Ala variant of 101 T2DM patients and 104 controls were amplified by PCR amplification and the extension reaction was performed using primer that adjacent to the single nucleotide polymorphic site in presence of two different dye-labeled terminators. The primer's specially extending reactions make the increase of their fluorescence polarization (FP) that mean special genotype. The variant frequencies of the two groups were compared. Results: We detected the Pro12Ala variant successfully by TDI-FP method and we found no significant association between this polymorphism and T2DM in case-control study. Conclusion: The TDI-FP technology is a new specific and sensitive method that is suitable for automatic detection of large number of clinical samples. Prol2Ala mutation in PPAR--@2 gene does not play a significant role in T2DM risk in Chinese population.
基金Supported by the National Natural Science Foundation of China (30630056)the Natural Science Foundation of Chongqing (2006BB5064)
文摘Atrial fibrillation (AF) is the most common arrhythmia with multi-factorial pathogenesis. A number of studies of genetic epidemiology have assessed the association of G112A (G38S) single nucleotide polymorphisms (SNPs) in Mink gene with AF in different populations. However, the results are inconsistent and inconclusive. We performed a Meta-analysis of the association between G112A polymorphisms of MinK gene and AF to estimate the magnitude of the gene effect. Six case-control studies with a combined 854 cases and 1079 controls were summarized. Subgroups in different races were separately analyzed. Heterogeneity and publication bias were also explored. When all groups were pooled, the individuals with G allele had an over 40% higher risk of AF compared with individuals with the A allele. The GG genotype (versus AA genotype) was found to be significant association with increased AF risk. The significant associations were also found in both dominant and recessive genetic model. For subgroup analysis, the results were consistent with above, except that the pooled OR for Chinese population was not significant in a recessive genetic model. In conclusion, G112A polymorphisms in Mink gene may have an important effect on the pathogenesis of AF. This warrants further investigation in large multi-center studies with precise design.
