CYP2C9 and CYP2C19 genetic polymorphisms: frequencies in the south Indian population

Abstract

The aim of the study was to establish the frequencies of CYP2C9*1, *2, *3 and CYP2C19*1, *2 and *3 in the south Indian population and to compare them with the inter-racial distribution of the CYP2C9 and CYP2C19 genetic polymorphisms. Genotyping analyses of CYP2C9 and CYP2C19 were conducted in unrelated, healthy volunteers from the three south Indian states of Andhra Pradesh, Karnataka and Kerala, by the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP). The allele frequencies of the populations of these three states were then pooled with our previous genotyping data of Tamilians (also in south India), to arrive at the distribution of CYP2C9 and CYP2C19 alleles in the south Indian population. Frequencies of CYP2C9 and CYP2C19 alleles and genotypes among various populations were compared using the two-tailed Fisher's exact test. The frequencies of CYP2C9*1, *2 and *3 in the south Indian population were 0.88 (95% CI 0.85-0.91), 0.04 (95% CI 0.02-0.06) and 0.08 (95% CI 0.06-0.11), respectively. The frequencies of CYP2C9 genotypes *1/*1, *1/*2, *1/*3, *2/*2, *2/*3 and *3/*3 were 0.78 (95% CI 0.74-0.82), 0.05 (95% CI 0.03-0.07), 0.15 (95% CI 0.12-0.18), 0.01 (95% CI 0.0-0.02), 0.01 (95% CI 0.0-0.02) and 0.0, respectively. CYP2C19*1, *2 and *3 frequencies were 0.64 (95% CI 0.60-0.68), 0.35 (95% CI 0.31-0.39) and 0.01 (95% CI 0.0-0.03), respectively. As a result of a significant heterogeneity, the data on CYP2C19 genotype frequencies were not pooled. The frequency of CYP2C9*2 mutant alleles in south Indians was higher than in Chinese and Caucasians, while CYP2C9*3 was similar to Caucasians. CYP2C19*2 was higher than in other major populations reported so far. The relatively high CYP2C19 poor-metabolizer genotype frequency of 12.6% indicates that over 28 million south Indians are poor metabolizers of CYP2C19 substrates.

Correlation of CYP2C19 genotype with plasma voriconazole levels: a preliminary retrospective study in Indians

“…The variation -806C [ T in the promoter region (CYP2C19*17) causes an increase in gene transcription and enzyme activity resulting in an ultra-rapid metabolism of voriconazole [25,26]. The allele frequency of 30, 18.1 and 0.9 % obtained for *2, *17 and *3 allele respectively in our study are in concurrence with those reported from other parts of India in the Clinical Pharmacogenetics Implementation Consortium (CPIC) [16,27]. Plasma voriconazole levels observed in our study group reflect a wide inter-individual variability and warrant the need for TDM.…”

Functional Characterization of Novel Allelic Variants of CYP2C9 Recently Discovered in Southeast Asians

“…CYP2C9*2 and CYP2C9*3 are the most common defective alleles in the white populations (11 and 8.4%, respectively) but have significantly lower frequencies in African populations (2.9 and 1.3%, respectively) and Eastern Asian populations such as Chinese (0 and 3.3%), Japanese (0 and 2.2%), and Koreans (0 and 1.1%, respectively) (Xie et al, 2001(Xie et al, , 2002. However, higher frequencies of these two alleles have been reported in Indian populations compared with Eastern Asians (4 -6% and 8 -13.8%) (Zainuddin et al, 2003;Jose et al, 2005). Similarly, recent studies from one of our laboratories (Zhao et al, 2004) reported frequencies of 4 and 11.5%, respectively, for the CYP2C9*2 and CYP2C9*3 alleles in Indians, 0 and 3.3% in Chinese, and 0 and 6.3% in Malays from Singapore who were receiving maintenance warfarin therapy.…”

A study on the impact of CYP2C19 genotype and platelet reactivity assay on patients undergoing PCI

“…Studies by Jose et al (2004), 20 Adithan et al (2003) 15 and Anichavezhi et al (2012) 16 demonstrated that variant 2 had higher presence in healthy Indian volunteer population compared to Caucasians (Table 5). 21,22 Based on a study with 112 subjects of Tamilian ethnicity, Adithan et al (2003) 15 reported an allele frequency of 0.37 for the variant 2 compared to 0.4 in our study.…”