Association of CYP2C9, CYP2C19, CYP2C8, CYP2A6, and CYP3A4 gene polymorphism with drug response in an Indian cohort of patients with type 2 diabetes mellitus

CYP2C9、CYP2C19、CYP2C8、CYP2A6 和 CYP3A4 基因多态性与印度 2 型糖尿病患者药物反应的相关性

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Abstract

PURPOSE: Type 2 Diabetes Mellitus (T2DM) affects over 500 million people worldwide and presents diverse therapeutic challenges due to variability in drug response. Cytochrome P450 (CYP450) polymorphisms play a pivotal role in shaping individual responses to medications by influencing how drugs are metabolized in the body. This study explored the association of CYP 450 Polymorphism with drug response in an Indian cohort of patients with diabetes mellitus. METHODOLOGY: A total of 144 T2 DM patients were stratified into the drug responders and non-responders based on their HbA1c values. The sociodemographic, clinical, and Genotype and polymorphism of CYP2C9, CYP2C19, CYP2C8, CYP2A6 and CYP3A4 were compared between drug responders and non-responders. Association of CYP Gene Polymorphism with Drug Response in patients with Type 2 diabetes Mellitus was studied using chi square test. RESULTS: Among the 144 Types 2 diabetes patients, results demonstrated that 66% responded to drug therapy. DNA analysis from 144 samples confirmed quality standards, and significant associations were found between drug response and polymorphisms in CYP2C9 (rs1934963, rs2298037, rs1057910) and CYP2C19 (rs11188072), with responders showing higher wild-type frequencies. No associations were found for CYP2C8, CYP2A6, or CYP3A4 SNPs. Differences in genotype distributions for CYP2C9 (P = 0.001), CYP2A6 (P = 0.03) and CYP2C19 (P = 0.037) genes between drug responders and non-responders were statistically significant. CONCLUSION: A significant association between drug response and polymorphisms in CYP2C9 and CYP2C19 was found. By analysing genotypic patterns among drug responders and non-responders, the study highlights the importance of pharmacogenetic screening in optimizing personalized diabetes care.

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