Genotype Phenotype Correlation of Genetic Polymorphism of PPAR Gamma Gene and Therapeutic Response to Pioglitazone in Type 2 Diabetes Mellitus- A Pilot Study

摘要

Introduction: Pro12Ala polymorphism is a missense mutationat codon 12 in peroxisome proliferator-activated receptor γ gene(PPARG). This polymorphism is known to be associated withincreased insulin sensitivity. Pioglitazone, a thiazolidinedione,is an anti-diabetic drug which acts as an agonist at PPAR γreceptor.Aim: To determine the association between Pro12Alapolymorphism of the PPARG and variation in therapeuticresponse to the PPARγ agonist, pioglitazone.Materials and Methods: The study was done as a hospitalbased pilot project in 30 patients with type 2 diabetes mellitus, ontreatment with sulfonylurea or metformin but without adequateglycaemic control. They were started on pioglitazone as addon therapy for a period of 12 weeks. The participants werecategorized as responders and non-responders based on thechange in HbA1C level after 12 weeks. Pro12Ala polymorphismwas analysed by polymerase chain reaction-restriction fragmentlength polymorphism.Statistical Analysis: Logistic regression analysis was done toevaluate the associations between age, baseline body weight,BMI, waist circumference, waist-hip ratio and Pro12Ala variantswith the response to pioglitazone. The p-value< 0.05 wasconsidered significant.Results: The frequency distributions of PPAR gammagenotypes were 80% for Pro/Pro and 20% for Pro/Ala in thestudy population. Among the study participants, 30% were nonresponders and 70% responders to pioglitazone. A significantlyhigher frequency of the polymorphism was detected in theresponders (p=0.005) compared to non-responders group.Conclusion: Our study suggests that there is a potentialassociation between Pro12Ala polymorphism and glycaemicresponse to pioglitazone.