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.
Subject(s)
Aryl Hydrocarbon Hydroxylases/genetics , Mixed Function Oxygenases/genetics , Polymorphism, Genetic , Adult , Cytochrome P-450 CYP2C19 , Cytochrome P-450 CYP2C9 , Female , Gene Frequency , Genetics, Population , Humans , India , Male , Polymerase Chain Reaction , Polymorphism, Restriction Fragment LengthABSTRACT
OBJECTIVE: To investigate the distribution of the homozygous null genotypes of GSTM1 and GSTT1 in the South Indian population. METHODS: Five hundred and seventeen unrelated natives of the South Indian states of Tamilnadu and Pondicherry (n=170), Kerala (n=122), Karnataka (n=110) and Andhra Pradesh (n=115) were analyzed for homozygous deletions of GSTM1 and GSTT1. A multiplex polymerase chain reaction method simultaneously detected both GSTM1 and GSTT1 homozygous null genotypes. The observed frequencies from the four groups were compared statistically with each other and the combined frequencies were compared with frequencies of other major populations previously reported in the literature. RESULTS: In South India, 30.4% (95% CI 26.4-34.3) lacked the GSTM1 gene, 16.8% (13.6-20.1) lacked the GSTT1 gene and 4.6% (3.0-6.8) lacked both the GSTM1 and GSTT1 genes. The highest frequency of GSTM1 null was observed in Karnataka (36.4%, 27.4-45.4), while Andhra Pradesh had the lowest frequency of the GSTM1 and GSTT1 combined double-null genotypes (1.7%, 0.21-6.2). CONCLUSION: The prevalence of the GSTM1 null genotype differed within India. The frequency of GSTM1 null in South Indians was significantly lower than that in Caucasians. The frequencies of both GSTM1 and GSTT1 null genotypes in South Indians were significantly lower than in the Japanese.
