Genetic polymorphisms of drug‐metabolizing phase I enzymes CYP2E1, CYP2A6 and CYP3A5 in South Indian population

Abstract

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 CYP2E1*1B, CYP2E1*5B and CYP2E1*6 alleles in South Indian population were 14.3, 1.3 and 22.4%, respectively. The frequencies of CYP2A6*2, CYP2A6*4A and CYP2A6*5 alleles were found to be 1, 8.9 and 0.7%, respectively. The distribution of CYP3A5*3 allele was 63.5%. There were no variant alleles of CYP3A5*2, CYP3A5*4 and CYP3A5*6 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.

Functional PstI/RsaI Polymorphisms in the CYP2E1 Gene among South Indian Populations

“…The c2 mutant allele frequency in study populations is 1.1-5.9% and is consistent with previous reports from India (Sikdar et al, 2003;Krishnakumar et al, 2012). The c2 mutant allele in South Indians was lower than in Chinese, Taiwanese, Japanese and Caucasians populations (Garte et al, 2001).…”

Single nucleotide polymorphism of CYP3A5*3 contributes to clopidogrel resistance in coronary artery disease patients among Tamilian population

“…The frequencies of AA, AG and GG genotypes of CYP3A5*3 were found to be 21, 45 and 34 %, respectively and also the alleleic frequencies were found to be 47.4 and 52.6 %. This is almost similar to the frequencies established in the south Indian population [17]. Thus the frequency of CYP3A5*3 in coronary artery disease patients were found to be in Hardy-Weinberg equilibrium.…”

“…The sample was centrifuged at 2,500 rpm for 10 min at 4°C and the genomic DNA was extracted from the blood using phenol chloroform extraction procedure. Further, genotyping was done by standard RT-PCR method [17]. The PCR samples of the homozygous and heterozygous mutants were selected randomly and sequenced for confirmation.…”

“…The defective allele frequency of CYP3A5*1 and *3 alleles in the Tamilian population were 37 % and 63 % respectively. The distribution of CYP3A5*1/*1 (AA), *1/*3 (AG) and *3/*3 (GG) genotypes were 15.2 %, 43.5 % and 41.3 % respectively [17]. The role of CYP2C19 genotypes on the clopidogrel metabolism has already been studied in our population in relation to clopidogrel response variability [18].…”

Polymorphisms of cytochrome P450 genes in three ethnic groups from Russia

“…For the representatives of the African population of Yoruba in Ibadan, Nigeria (YRI) this allele does not occur at all (HapMap). In the South Indian population it was only 1.3% (32). The frequency of allele CYP2E1*5B of the CYP2E1 ranged from 2.66% in Russians to 6.8% in Bashkirs.…”