title: Genotype Phenotype Correlation of Genetic Polymorphism of PPAR Gamma Gene and Therapeutic Response to Pioglitazone in Type 2 Diabetes Mellitus- A Pilot Study.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To determine the association between Pro12Ala polymorphism of the PPARG and variation in therapeutic response to the PPARγ agonist, pioglitazone.
  
  
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Our study suggests that there is a potential association between Pro12Ala polymorphism and glycaemic response to pioglitazone.
authors.affiliation: Assistant Professor, Department of Pharmacology, PSG IMSR , Tamilnadu, India .
authors.forename: S Shanmuga
authors.initials: SS
authors.lastname: Priya
authors.affiliation: Professor, Department of Pharmacology, PSG IMSR , Tamilnadu, India .
authors.forename: Ramalingam
authors.initials: R
authors.lastname: Sankaran
authors.affiliation: Professor, Department of Community Medicine, PSG IMSR , Tamilnadu, India .
authors.forename: Sudha
authors.initials: S
authors.lastname: Ramalingam
authors.affiliation: Associate Professor, Department of Molecular medicine, PSG IMSR , Tamilnadu, India .
authors.forename: Thiagarajan
authors.initials: T
authors.lastname: Sairam
authors.affiliation: Professor, Department of Internal Medicine, PSG IMSR , Tamilnadu, India .
authors.forename: L S
authors.initials: LS
authors.lastname: Somasundaram
keywords: Glycaemic response; Pharmacogenetic; Pioglitazone; Pro12Ala; South India