Cytochromes P450(CYPs)play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including chemotherapeutics.The gene expr...Cytochromes P450(CYPs)play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including chemotherapeutics.The gene expression and enzyme activity of CYPs are variable between individuals,which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics,as well as differences in the efficacy and toxicity of clinically used drugs.This research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients,as well as the clinical outcome after receiving cyclophosphamide chemotherapy.DNA was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex-and age-matched healthy individuals.The presence of the CYP2B6*9(G516T)polymorphism was examined by PCR-based allele specific amplification(ASA).Patients were further indicated for receiving chemotherapy,and then they were followed up.The CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models,comprising allelic(T-allele vs.G-allele,OR=4.8,p<0.001)and dominant(GT+TT vs.GG,OR=5.4,p<0.001)models.Following cyclophosphamide chemotherapy,we found that the patients with variant genotypes(GT+TT)were less likely to achieve remission compared to those with the wild-type genotype(GG),with a response percentage of(37.5%vs.83%,respectively).In conclusion,our findings showed that the CYP2B6*9(G516T)polymorphism is associated with B-CLL susceptibility among Egyptian patients.This variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.展开更多
目的:探讨中国人群中IL-6基因启动子中单核苷酸多态性与HBV感染的遗传易感性关联.方法:提取160例HBV感染者及212例健康献血者外周血基因组DNA,用PCR-RFLP方法检测两组人群中G-174C、G-572C和G-597A三个多态性位点的基因型.性别、吸烟、...目的:探讨中国人群中IL-6基因启动子中单核苷酸多态性与HBV感染的遗传易感性关联.方法:提取160例HBV感染者及212例健康献血者外周血基因组DNA,用PCR-RFLP方法检测两组人群中G-174C、G-572C和G-597A三个多态性位点的基因型.性别、吸烟、饮酒以及Hardy-Weinberg等采用Chi-square Test检测,多态性与HBV感染者风险关联及亚组关联的统计学分析采用非条件Logistic回归并同时校正混杂因素.结果:PCR-RFLP检测结果显示:IL-6基因启动子中G-174C和G-597A两个位点在中国人群中不存在多态性,而G-572C处的多态性在人群中普遍存在,其多态性位点等位基因频率分布符合Hardy-Weinberg平衡定律.统计分析表明该位点的多态性在两组人群中有明显的差异(G/C vs G/G,OR=2.65,P<0.05;C/C vs G/G,OR=3.31,P<0.05);亚组分析中表明<30岁的年龄组中差异显著(G/G vs G/C或C/C,OR=16.92,P<0.05).结论:在中国汉族人群中,IL-6基因启动子中-572处的多态性对于乙型肝炎的发生有着显著的易患关系,同时年龄对于这种易感关联有着协同作用.展开更多
文摘Cytochromes P450(CYPs)play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including chemotherapeutics.The gene expression and enzyme activity of CYPs are variable between individuals,which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics,as well as differences in the efficacy and toxicity of clinically used drugs.This research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients,as well as the clinical outcome after receiving cyclophosphamide chemotherapy.DNA was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex-and age-matched healthy individuals.The presence of the CYP2B6*9(G516T)polymorphism was examined by PCR-based allele specific amplification(ASA).Patients were further indicated for receiving chemotherapy,and then they were followed up.The CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models,comprising allelic(T-allele vs.G-allele,OR=4.8,p<0.001)and dominant(GT+TT vs.GG,OR=5.4,p<0.001)models.Following cyclophosphamide chemotherapy,we found that the patients with variant genotypes(GT+TT)were less likely to achieve remission compared to those with the wild-type genotype(GG),with a response percentage of(37.5%vs.83%,respectively).In conclusion,our findings showed that the CYP2B6*9(G516T)polymorphism is associated with B-CLL susceptibility among Egyptian patients.This variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.
文摘目的:探讨中国人群中IL-6基因启动子中单核苷酸多态性与HBV感染的遗传易感性关联.方法:提取160例HBV感染者及212例健康献血者外周血基因组DNA,用PCR-RFLP方法检测两组人群中G-174C、G-572C和G-597A三个多态性位点的基因型.性别、吸烟、饮酒以及Hardy-Weinberg等采用Chi-square Test检测,多态性与HBV感染者风险关联及亚组关联的统计学分析采用非条件Logistic回归并同时校正混杂因素.结果:PCR-RFLP检测结果显示:IL-6基因启动子中G-174C和G-597A两个位点在中国人群中不存在多态性,而G-572C处的多态性在人群中普遍存在,其多态性位点等位基因频率分布符合Hardy-Weinberg平衡定律.统计分析表明该位点的多态性在两组人群中有明显的差异(G/C vs G/G,OR=2.65,P<0.05;C/C vs G/G,OR=3.31,P<0.05);亚组分析中表明<30岁的年龄组中差异显著(G/G vs G/C或C/C,OR=16.92,P<0.05).结论:在中国汉族人群中,IL-6基因启动子中-572处的多态性对于乙型肝炎的发生有着显著的易患关系,同时年龄对于这种易感关联有着协同作用.
文摘MeLTI6A(Manihot esculenta low temperature inducible 6A)是木薯低温干旱诱导基因,本研究从MeLTI6A的序列出发,利用电子克隆设计引物进行PCR扩增的方法获得该基因的启动子,其序列共1 304 bp。生物信息学分析发现该启动子中具有真核生物典型的核心启动子区(TATA-box和CAAT-box),并利用α-互补,蓝白斑筛选原理验证了该启动子核心序列具有活性;该启动子具有与干旱胁迫相关的激素类(如脱落酸、乙烯)的响应元件和逆境胁迫(如低温、干旱胁迫)的响应元件;还具有与木薯组织特异表达相关的调控元件和其它光响应元件;并通过Real time PCR检测了低温胁迫(4℃)下的木薯组培苗中MeLTI6A的表达变化,说明了该启动子区的低温胁迫顺式作用响应元件可能调节MeLIT6A在低温胁迫下的表达。这些说明木薯的MeLIT6A基因可能是通过对干旱胁迫激素信号响应以及逆境胁迫响应起作用,使木薯获得一定的抗胁迫的能力,同时还可能参与了木薯相关组织发育过程的调控。本研究有利于对MeLTI6A基因抗逆境胁迫功能的理解,为探索木薯高效抗逆的分子机制作初步研究。
