Pharmacogenetics of sulfonylurea: Presence of CYP2C9*2, CYP2C9*3 and a novel allele, CYP2C9*61, in Type 2 diabetes patients under sulfonylurea therapy

Abstract

CYP2C9 is an important member of the cytochrome P450 gene family involved in the metabolism of 15% of the drugs including an oral antidiabetic agent sulfonylurea. This study aims to investigate the frequency of CYP2C9*2 and CYP2C9*3 alleles of the gene in the sulfonylurea treated diabetic subjects in Pakistan. Briefly, total 105 patients were included in the study and segregated as control (24) and test (81) based on the clinical manifestations after taking sulfonylurea. Genomic DNA was extracted from blood of the subjects and amplified using CYP2C9 specific primers for exon 3 and exon 7 and then subjected to DNA sequencing. Alignment of the sequences with the reference sequence shows presence of CYP2C9*3/*3, CYP2C9*1/*3 and CYP2C9*1/*2 genotypes in the test cases but only the latter two were found in the control cases. In addition a novel allele, CYP2C9*61 in the heterozygous state, was also identified frequently in the test cases. Molecular structure comparison also showed variations in the structural features of protein encoded by the allelic variants. To the best of our knowledge, the present data is the first report for CYP2C9 allelic variations in the indigenous diabetic subjects and also report the existence of novel allelic variant of CYP2C9, CYP2C9*61.