ICMR Centre for Advance Research in Pharmacogenomics, Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education & Research, Pondicherry 605 006, India.
Fundam Clin Pharmacol. 2012 Apr;26(2):295-306. doi: 10.1111/j.1472-8206.2010.00917.x. Epub 2011 Jan 25.
CYP2E1, CYP2A6 and CYP3A5 enzymes belong to phase I group of drug-metabolizing enzymes, which are involved in the metabolism of various compounds and xenobiotics. Presence of polymorphisms in the genes coding for these enzymes results in interindividual variations in drug metabolism, therapeutic response and susceptibility towards various diseases. The frequencies of these variants in genes differ considerably between ethnic groups. This study was carried out to estimate the allele and genotype frequencies of common variants in CYP2E1, CYP2A6 and CYP3A5 in South Indian population. Six hundred and fifty-two unrelated healthy volunteers of South Indian origin (Andhra Pradesh, Karnataka, Kerala and Tamil Nadu) were included in this study. Polymerase chain reaction-restriction fragment length polymorphism, allele-specific PCR, real-time PCR, SNaPshot and gene sequencing methods were used for the identification of gene polymorphisms. The frequencies of CYP2E11B, CYP2E15B and CYP2E16 alleles in South Indian population were 14.3, 1.3 and 22.4%, respectively. The frequencies of CYP2A62, CYP2A64A and CYP2A65 alleles were found to be 1, 8.9 and 0.7%, respectively. The distribution of CYP3A53 allele was 63.5%. There were no variant alleles of CYP3A52, CYP3A54 and CYP3A56 in South Indian population. The frequencies of CYP2E1, CYP2A6 and CYP3A5 in the South Indian population are distinct from Caucasians, Chinese, Japanese, African Americans and other compared populations. This is the first study conducted in the South Indian population with a larger sample size. The findings of our study provide the basic genetic information for further pharmacogenomic investigations in the population.
CYP2E1、CYP2A6 和 CYP3A5 酶属于药物代谢酶的 I 相酶组，参与各种化合物和外源性物质的代谢。编码这些酶的基因中的多态性导致药物代谢、治疗反应和对各种疾病的易感性存在个体间差异。这些基因变体的频率在不同种族之间有很大差异。本研究旨在评估 CYP2E1、CYP2A6 和 CYP3A5 常见变体在印度南部人群中的等位基因和基因型频率。本研究纳入了 652 名来自印度南部（安得拉邦、卡纳塔克邦、喀拉拉邦和泰米尔纳德邦）的无亲缘关系的健康志愿者。使用聚合酶链反应-限制性片段长度多态性、等位基因特异性 PCR、实时 PCR、SNaPshot 和基因测序方法来鉴定基因多态性。在印度南部人群中，CYP2E11B、CYP2E15B 和 CYP2E16 等位基因的频率分别为 14.3%、1.3%和 22.4%。CYP2A62、CYP2A64A 和 CYP2A65 等位基因的频率分别为 1%、8.9%和 0.7%。CYP3A53 等位基因的分布为 63.5%。在印度南部人群中没有 CYP3A52、CYP3A54 和 CYP3A56 变体等位基因。CYP2E1、CYP2A6 和 CYP3A5 在印度南部人群中的频率与高加索人、中国人、日本人、非裔美国人以及其他比较人群不同。这是在印度南部人群中进行的第一项具有更大样本量的研究。本研究的结果为该人群的进一步药物基因组学研究提供了基本的遗传信息。
