Rifampin, a member of the rifamycin class of antibiotics, is well known for its ability to activate the pregnant X receptor and induce drug-metabolizing enzymes and transporters. Available data suggest rifampin entry ...Rifampin, a member of the rifamycin class of antibiotics, is well known for its ability to activate the pregnant X receptor and induce drug-metabolizing enzymes and transporters. Available data suggest rifampin entry into hepatocytes is mediated by OATP1B1. Accordingly, it is therefore plausible that modulation of the intracellular concentration of rifampin by OATP1B1 genetic polymorphisms would influence the degree of CYP3A induction. AIM: To study the association between haplotypes of the SLCO1B1 and the rifampicin-mediated inducible CYP3A4 activity. A single-point determination of midazolam plasma concentration method was developed to assess the constitutive and inducible CYP3A4 activity. A pharmacokinetic study of a single dose of 450 mg rifampicin was conducted to evaluate the mechanism of rifampicin-midazolam interaction in different SLCO1B1 genotypic subjects. METHODS: Twenty-three healthy volunteers with different SLCO1B1 haplotypes (7 for SLCO1B1*1a/*1a, 7 for SLCO1B1*1b/*1b, 7 for SLCO1B1*1b/*15 and 2 for SLCO1B1*15/*15) were enrolled in this study. Each was given a single oral dose of 7.5 mg midazolam on day 0 and day 6. Rifampicin of 450 mg was given from day 1 to day 5. Plasma concentrations of midazolam were measured for up to 8 hours by LC-MS, and its pharmacokinetic parameters were analyzed. Plasma concentrations of a single oral dose of 450 mg rifampicin were measured for up to 12 hours. RESULTS: A significant correlation (r2=0.763, P<0.001, n=23) was found between AUC(0-∞) and the single plasma concentration of midazolam at 2.5 hour (C2.5 h). The 2.5 h midazolam measurement was an optimal predictor of CYP3A phenotype. However, the percentage reduction of AUC(0-∞) or C2.5 h in different SLCO1B1 haplotypes was not significantly different. The pharmacokinetics parameters of rifampin were not significantly different between the 521T>C mutant group and the control group. CONCLUSION: A single blood concentration at 2.5 h after 7.5 mg oral midazolam intake can be used to predict CYP3A activity. The SLCO1B1 haplotypes do not influence the extent of inducible CYP3A activity by rifampin. SLCO1B1 genotypes has no significant impact on the disposition of rifampin in vivo.展开更多
目的:探讨Tim-1基因4个SNP位点及单倍型与宁夏地区回族人群类风湿性关节炎(RA)的关联性,旨在为RA的早期预防提供理论依据。方法:采用序列特异性引物聚合酶链式反应(SSP-PCR)及限制性片段长度多态性(PCR-RFLP)2种方法对108例RA患者及104...目的:探讨Tim-1基因4个SNP位点及单倍型与宁夏地区回族人群类风湿性关节炎(RA)的关联性,旨在为RA的早期预防提供理论依据。方法:采用序列特异性引物聚合酶链式反应(SSP-PCR)及限制性片段长度多态性(PCR-RFLP)2种方法对108例RA患者及104例健康个体Tim-1基因-1637A>G、-1454G>A、-416G>C和-232A>G共4个SNP位点进行检测,对各基因位点基因型频数、等位基因频数及单倍型分布情况进行比较和分析。结果:健康对照组与RA患者组-1637、-232位点基因型频数分布差异有统计学意义,在RA患者中-1637位点等位基因A的频数高于等位基因G(P<0.01)。4个位点共检出15种单倍型,单倍型AGCA(OR值9.611,95% CI 3.13～29.52)、AGCG(OR值4.361,95% CI 2.12～8.96)在宁夏回族RA患者组中的频数高于健康人群(P<0.01);而单倍型GGCA(OR值0.374,95% CI 0.22～0.64)、GGCG(OR值0.199,95% CI 0.08～0.49)及GAGA(OR值0.023,95%CI 0.002～0.26)在宁夏回族人群RA患者组中的频数低于健康对照组(P<0.01)。结论:-1637位点A>G的突变与宁夏回族人群RA发生有关,等位基因A的存在可增加RA发病风险,而等位基因G对RA的发生具有保护作用;AGCA、AGCG这2种单倍型可增加宁夏回族人群RA发生的风险,而单倍型GGCA、GGCG、GAGA对宁夏回族人群RA的发生具有保护作用。展开更多
为探究盐胁迫下水稻地上部和根部Na^(+)、K^(+)含量和分布对其生物量累积和苗期耐盐性的影响,利用125 mmol/L Na Cl对51份不同类型水稻种质资源进行胁迫处理,测定5个形态学指标:耐盐级别、相对根长、相对地上部干重、相对根干重和地上...为探究盐胁迫下水稻地上部和根部Na^(+)、K^(+)含量和分布对其生物量累积和苗期耐盐性的影响,利用125 mmol/L Na Cl对51份不同类型水稻种质资源进行胁迫处理,测定5个形态学指标:耐盐级别、相对根长、相对地上部干重、相对根干重和地上部含水量;6个离子指标:地上部Na^(+)含量、根系Na^(+)含量、地上部K^(+)含量、根系K^(+)含量、地上部Na^(+)/K^(+)和根系Na^(+)/K^(+),共11个耐盐相关指标。在主成分分析基础上,利用隶属函数和标准差系数赋予权重法获得水稻苗期耐盐性综合评价值(D值)。利用特异引物扩增SKC1基因编码区进行测序、比对和单倍型分析。结果表明:除相对根长外,地上部Na^(+)含量与其余4个形态学指标呈极显著负相关,耐盐级别与地上部Na^(+)含量、根系Na^(+)含量和地上部Na^(+)/K^(+)均呈极显著负相关,耐盐级别、相对地上部干重、相对根干重、地上部含水量4个指标两两之间均呈极显著正相关。利用SPSS主成分分析将11个单项指标转换为4个主成分,累计贡献率达82.093%。依据PC1中各指标的载荷系数,筛选出相对地上部干重、耐盐级别、相对根干重、地上部Na^(+)含量、地上部Na^(+)/K^(+)和根系Na^(+)含量6个重要指标;结合综合评价D值与这6个指标的线性回归分析,发现耐盐级别和地上部Na^(+)/K^(+)的系数较大,分别是影响水稻苗期耐盐性的形态学和离子平衡关键因子。通过对51份水稻种质资源SKC1编码区序列比对,共检测到9种不同的单倍型。其中源于越光的单倍型(Hap1)为粳稻种质资源的优势等位基因;源于Nona Bokra的单倍型(Hap7)为籼稻和Aus的优势等位基因。本研究结果可从离子平衡层面为耐盐水稻资源筛选与鉴定提供理论依据。展开更多
【目的】通过分析棉花枯萎病菌的遗传多样性,探究新疆棉花枯萎病菌株的分群及其演化。【方法】2022年在新疆不同植棉区共分离出22株棉花枯萎病菌株,对延伸因子1α(elongation factor-1α,EF-1α)和β微管蛋白基因进行扩增、测序,并从美...【目的】通过分析棉花枯萎病菌的遗传多样性,探究新疆棉花枯萎病菌株的分群及其演化。【方法】2022年在新疆不同植棉区共分离出22株棉花枯萎病菌株,对延伸因子1α(elongation factor-1α,EF-1α)和β微管蛋白基因进行扩增、测序,并从美国国立生物技术信息中心(National Center for Biotechnology Information,NCBI)数据库获取36个棉花枯萎病菌株的相关基因序列信息。基于上述基因序列分别进行系统进化分析和单倍型分析。【结果】基于57条EF-1α基因序列的进化树分析表明,棉花枯萎病菌可分为3大群,第1大群包含来自新疆、河北和澳大利亚的共31个枯萎病菌株,该大群可分成4个亚群;第2大群包含25个枯萎病菌株,构成比较复杂,可分成3个亚群;第3大群仅包含美国菌株LA140。基于28条β微管蛋白基因序列的进化树分析表明,本次分离的新疆棉花枯萎病菌株与棉花枯萎病菌7号和8号生理小种不同。根据EF-1α基因序列构建的单倍型网络将棉花枯萎病菌株分为19个单倍型,新疆21个棉花枯萎病菌株归属于有共同起源的5种单倍型。【结论】本研究分离的新疆棉花枯萎病菌株与已报道的棉花枯萎病菌1~8号生理小种均不相同,但与河北菌株的亲缘关系较近。EF-1α单倍型分析表明,本研究中的所有棉花枯萎病菌均从1号生理小种演化而来。展开更多
文摘Rifampin, a member of the rifamycin class of antibiotics, is well known for its ability to activate the pregnant X receptor and induce drug-metabolizing enzymes and transporters. Available data suggest rifampin entry into hepatocytes is mediated by OATP1B1. Accordingly, it is therefore plausible that modulation of the intracellular concentration of rifampin by OATP1B1 genetic polymorphisms would influence the degree of CYP3A induction. AIM: To study the association between haplotypes of the SLCO1B1 and the rifampicin-mediated inducible CYP3A4 activity. A single-point determination of midazolam plasma concentration method was developed to assess the constitutive and inducible CYP3A4 activity. A pharmacokinetic study of a single dose of 450 mg rifampicin was conducted to evaluate the mechanism of rifampicin-midazolam interaction in different SLCO1B1 genotypic subjects. METHODS: Twenty-three healthy volunteers with different SLCO1B1 haplotypes (7 for SLCO1B1*1a/*1a, 7 for SLCO1B1*1b/*1b, 7 for SLCO1B1*1b/*15 and 2 for SLCO1B1*15/*15) were enrolled in this study. Each was given a single oral dose of 7.5 mg midazolam on day 0 and day 6. Rifampicin of 450 mg was given from day 1 to day 5. Plasma concentrations of midazolam were measured for up to 8 hours by LC-MS, and its pharmacokinetic parameters were analyzed. Plasma concentrations of a single oral dose of 450 mg rifampicin were measured for up to 12 hours. RESULTS: A significant correlation (r2=0.763, P<0.001, n=23) was found between AUC(0-∞) and the single plasma concentration of midazolam at 2.5 hour (C2.5 h). The 2.5 h midazolam measurement was an optimal predictor of CYP3A phenotype. However, the percentage reduction of AUC(0-∞) or C2.5 h in different SLCO1B1 haplotypes was not significantly different. The pharmacokinetics parameters of rifampin were not significantly different between the 521T>C mutant group and the control group. CONCLUSION: A single blood concentration at 2.5 h after 7.5 mg oral midazolam intake can be used to predict CYP3A activity. The SLCO1B1 haplotypes do not influence the extent of inducible CYP3A activity by rifampin. SLCO1B1 genotypes has no significant impact on the disposition of rifampin in vivo.
文摘目的:探讨Tim-1基因4个SNP位点及单倍型与宁夏地区回族人群类风湿性关节炎(RA)的关联性,旨在为RA的早期预防提供理论依据。方法:采用序列特异性引物聚合酶链式反应(SSP-PCR)及限制性片段长度多态性(PCR-RFLP)2种方法对108例RA患者及104例健康个体Tim-1基因-1637A>G、-1454G>A、-416G>C和-232A>G共4个SNP位点进行检测,对各基因位点基因型频数、等位基因频数及单倍型分布情况进行比较和分析。结果:健康对照组与RA患者组-1637、-232位点基因型频数分布差异有统计学意义,在RA患者中-1637位点等位基因A的频数高于等位基因G(P<0.01)。4个位点共检出15种单倍型,单倍型AGCA(OR值9.611,95% CI 3.13～29.52)、AGCG(OR值4.361,95% CI 2.12～8.96)在宁夏回族RA患者组中的频数高于健康人群(P<0.01);而单倍型GGCA(OR值0.374,95% CI 0.22～0.64)、GGCG(OR值0.199,95% CI 0.08～0.49)及GAGA(OR值0.023,95%CI 0.002～0.26)在宁夏回族人群RA患者组中的频数低于健康对照组(P<0.01)。结论:-1637位点A>G的突变与宁夏回族人群RA发生有关,等位基因A的存在可增加RA发病风险,而等位基因G对RA的发生具有保护作用;AGCA、AGCG这2种单倍型可增加宁夏回族人群RA发生的风险,而单倍型GGCA、GGCG、GAGA对宁夏回族人群RA的发生具有保护作用。
文摘为探究盐胁迫下水稻地上部和根部Na^(+)、K^(+)含量和分布对其生物量累积和苗期耐盐性的影响,利用125 mmol/L Na Cl对51份不同类型水稻种质资源进行胁迫处理,测定5个形态学指标:耐盐级别、相对根长、相对地上部干重、相对根干重和地上部含水量;6个离子指标:地上部Na^(+)含量、根系Na^(+)含量、地上部K^(+)含量、根系K^(+)含量、地上部Na^(+)/K^(+)和根系Na^(+)/K^(+),共11个耐盐相关指标。在主成分分析基础上,利用隶属函数和标准差系数赋予权重法获得水稻苗期耐盐性综合评价值(D值)。利用特异引物扩增SKC1基因编码区进行测序、比对和单倍型分析。结果表明:除相对根长外,地上部Na^(+)含量与其余4个形态学指标呈极显著负相关,耐盐级别与地上部Na^(+)含量、根系Na^(+)含量和地上部Na^(+)/K^(+)均呈极显著负相关,耐盐级别、相对地上部干重、相对根干重、地上部含水量4个指标两两之间均呈极显著正相关。利用SPSS主成分分析将11个单项指标转换为4个主成分,累计贡献率达82.093%。依据PC1中各指标的载荷系数,筛选出相对地上部干重、耐盐级别、相对根干重、地上部Na^(+)含量、地上部Na^(+)/K^(+)和根系Na^(+)含量6个重要指标;结合综合评价D值与这6个指标的线性回归分析,发现耐盐级别和地上部Na^(+)/K^(+)的系数较大,分别是影响水稻苗期耐盐性的形态学和离子平衡关键因子。通过对51份水稻种质资源SKC1编码区序列比对,共检测到9种不同的单倍型。其中源于越光的单倍型(Hap1)为粳稻种质资源的优势等位基因;源于Nona Bokra的单倍型(Hap7)为籼稻和Aus的优势等位基因。本研究结果可从离子平衡层面为耐盐水稻资源筛选与鉴定提供理论依据。
文摘【目的】通过分析棉花枯萎病菌的遗传多样性,探究新疆棉花枯萎病菌株的分群及其演化。【方法】2022年在新疆不同植棉区共分离出22株棉花枯萎病菌株,对延伸因子1α(elongation factor-1α,EF-1α)和β微管蛋白基因进行扩增、测序,并从美国国立生物技术信息中心(National Center for Biotechnology Information,NCBI)数据库获取36个棉花枯萎病菌株的相关基因序列信息。基于上述基因序列分别进行系统进化分析和单倍型分析。【结果】基于57条EF-1α基因序列的进化树分析表明,棉花枯萎病菌可分为3大群,第1大群包含来自新疆、河北和澳大利亚的共31个枯萎病菌株,该大群可分成4个亚群;第2大群包含25个枯萎病菌株,构成比较复杂,可分成3个亚群;第3大群仅包含美国菌株LA140。基于28条β微管蛋白基因序列的进化树分析表明,本次分离的新疆棉花枯萎病菌株与棉花枯萎病菌7号和8号生理小种不同。根据EF-1α基因序列构建的单倍型网络将棉花枯萎病菌株分为19个单倍型,新疆21个棉花枯萎病菌株归属于有共同起源的5种单倍型。【结论】本研究分离的新疆棉花枯萎病菌株与已报道的棉花枯萎病菌1~8号生理小种均不相同,但与河北菌株的亲缘关系较近。EF-1α单倍型分析表明,本研究中的所有棉花枯萎病菌均从1号生理小种演化而来。
