Genetic variations and haplotypes of the 5′ regulatory region of CYP2C19 in South Indian population

CYP2C19 is expressed polymorphically with about 21 variant alleles. Genotype-phenotype association studies, of CYP2C19 have shown marked deviations, suggesting the presence of other variations in the intronic and 5′ regulatory region affecting its expression. This study aims to identify the genetic polymorphisms\ and construction of haplotypes of variations in 5′ regulatory region of CYP2C19 among the South Indian population. CYP2C19 5′ regulatory region was amplified and sequenced from the DNA of 58 healthy volunteers of South Indian origin. Genetic analysis revealed the existence of 14 variations including eight novel ones in the 5′ regulatory region. Identified novel variations and their percentage frequencies were: -779A>C (16.4), -828T>A (2.6), -934del>T (3.5), -1051T>C (1.72), -1289T>G (3.4), - 1442T>C (12.1), -1498T>G (25.0) and -1558T>G (2.6). The reported variations found in the study population and their frequencies were: -98T > C (28.4), -806C > T (2.6), - 833del > T (9.5), 889T > G (10.3), - 1041A> G (100.0) and - 1418C > T (1.7). The two known non synonymous single nucleotide polymorphisms, 681G>A (*2 allele) and 636G>A (*3 allele) were detected at 0.371 and 0.025 frequencies, respectively. Forty three haplotypes were constructed and linkage disequilibrium analysis showed strong linkage between several variations identified in the gene. Fourteen polymorphisms including 8 novel ones in CYP2C19 5′ flanking region are reported for the first time in an Indian population from South India. Results from this study provide additional information for genotyping of CYP2C19 in the South Indian population and probably in the Indian population.