S Shanmuga Priya1, Ramalingam Sankaran2, Sudha Ramalingam3, Thiagarajan Sairam4, L S Somasundaram5. 1. Assistant Professor, Department of Pharmacology, PSG IMSR , Tamilnadu, India . 2. Professor, Department of Pharmacology, PSG IMSR , Tamilnadu, India . 3. Professor, Department of Community Medicine, PSG IMSR , Tamilnadu, India . 4. Associate Professor, Department of Molecular medicine, PSG IMSR , Tamilnadu, India . 5. Professor, Department of Internal Medicine, PSG IMSR , Tamilnadu, India .
Abstract
INTRODUCTION: Pro12Ala polymorphism is a missense mutation at codon 12 in peroxisome proliferator-activated receptor γ gene (PPARG). This polymorphism is known to be associated with increased insulin sensitivity. Pioglitazone, a thiazolidinedione, is an anti-diabetic drug which acts as an agonist at PPAR γ receptor. AIM: To determine the association between Pro12Ala polymorphism of the PPARG and variation in therapeutic response to the PPARγ agonist, pioglitazone. MATERIALS AND METHODS: The study was done as a hospital based pilot project in 30 patients with type 2 diabetes mellitus, on treatment with sulfonylurea or metformin but without adequate glycaemic control. They were started on pioglitazone as add on therapy for a period of 12 weeks. The participants were categorized as responders and non-responders based on the change in HbA1C level after 12 weeks. Pro12Ala polymorphism was analysed by polymerase chain reaction-restriction fragment length polymorphism. STATISTICAL ANALYSIS: Logistic regression analysis was done to evaluate the associations between age, baseline body weight, BMI, waist circumference, waist-hip ratio and Pro12Ala variants with the response to pioglitazone. The p-value< 0.05 was considered significant. RESULTS: The frequency distributions of PPAR gamma genotypes were 80% for Pro/Pro and 20% for Pro/Ala in the study population. Among the study participants, 30% were non-responders and 70% responders to pioglitazone. A significantly higher frequency of the polymorphism was detected in the responders (p=0.005) compared to non-responders group. CONCLUSION: Our study suggests that there is a potential association between Pro12Ala polymorphism and glycaemic response to pioglitazone.
INTRODUCTION: Pro12Ala polymorphism is a missense mutation at codon 12 in peroxisome proliferator-activated receptor γ gene (PPARG). This polymorphism is known to be associated with increased insulin sensitivity. Pioglitazone, a thiazolidinedione, is an anti-diabetic drug which acts as an agonist at PPAR γ receptor. AIM: To determine the association between Pro12Ala polymorphism of the PPARG and variation in therapeutic response to the PPARγ agonist, pioglitazone. MATERIALS AND METHODS: The study was done as a hospital based pilot project in 30 patients with type 2 diabetes mellitus, on treatment with sulfonylurea or metformin but without adequate glycaemic control. They were started on pioglitazone as add on therapy for a period of 12 weeks. The participants were categorized as responders and non-responders based on the change in HbA1C level after 12 weeks. Pro12Ala polymorphism was analysed by polymerase chain reaction-restriction fragment length polymorphism. STATISTICAL ANALYSIS: Logistic regression analysis was done to evaluate the associations between age, baseline body weight, BMI, waist circumference, waist-hip ratio and Pro12Ala variants with the response to pioglitazone. The p-value< 0.05 was considered significant. RESULTS: The frequency distributions of PPAR gamma genotypes were 80% for Pro/Pro and 20% for Pro/Ala in the study population. Among the study participants, 30% were non-responders and 70% responders to pioglitazone. A significantly higher frequency of the polymorphism was detected in the responders (p=0.005) compared to non-responders group. CONCLUSION: Our study suggests that there is a potential association between Pro12Ala polymorphism and glycaemic response to pioglitazone.
Entities:
Keywords:
Glycaemic response; Pharmacogenetic; Pioglitazone; Pro12Ala; South India
Authors: E D Rosen; P Sarraf; A E Troy; G Bradwin; K Moore; D S Milstone; B M Spiegelman; R M Mortensen Journal: Mol Cell Date: 1999-10 Impact factor: 17.970
Authors: Ornella Ludovico; Fabio Pellegrini; Rosa Di Paola; Antonio Minenna; Sandra Mastroianno; Marina Cardellini; Maria Adelaide Marini; Francesco Andreozzi; Olga Vaccaro; Giorgio Sesti; Vincenzo Trischitta Journal: Obesity (Silver Spring) Date: 2007-05 Impact factor: 5.002
Authors: Myriam Fornage; David R Jacobs; Michael W Steffes; Myron D Gross; Molly S Bray; Pamela J Schreiner Journal: Metabolism Date: 2005-07 Impact factor: 8.694
Authors: S S Deeb; L Fajas; M Nemoto; J Pihlajamäki; L Mykkänen; J Kuusisto; M Laakso; W Fujimoto; J Auwerx Journal: Nat Genet Date: 1998-11 Impact factor: 38.330