Genotype Phenotype Correlation of Genetic Polymorphism of PPAR Gamma Gene and Therapeutic Response to Pioglitazone in Type 2 Diabetes Mellitus- A Pilot Study
Published: February 1, 2016 | DOI: https://doi.org/10.7860/JCDR/2016/.7331
S. Shanmuga Priya, Ramalingam Sankaran, Sudha Ramalingam, Thiagarajan Sairam, LS Somasundaram
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.
Correspondence
Dr. S. Shanmuga Priya,
PSG Institute of Medical Sciences & Research Off Avinashi Road, Peelamedu, Coimbatore-641004, Tamilnadu, India.
E-mail : somasundaram999@rediffmail.com
Introduction: Pro12Ala polymorphism is a missense mutation at codon 12 in peroxisome proliferator-activated receptor ? 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 ? receptor.
Aim: To determine the association between Pro12Ala polymorphism of the PPARG and variation in therapeutic response to the PPAR? 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.
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