Effect of PPARγ2 gene polymorphism (Pro12Ala) on HbA1C and its association with BMI in Type 2 diabetes subjects from Western India

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 796-817-Diabetes Genetics & Epidemiology
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-800
Avisek Majumder*1, Jayesh J Sheth1, Frenny Sheth1, Manan Patel1, Bhavik Doshi1, Navneet N Shah2, Premal Thakor3 and Rama Vaidya4
1Institute of Human Genetics, Ahmedabad, India, 2Sterling hospital, Ahmedabad, India, 3Gujarat Diabetes Association, Ahmedabad, India, 4Medical Research Centre- Kasturba Health Society, Mumbai, India
Background:  Peroxisome Proliferator Activated Receptor γ2 (PPARγ2) is a transcription factor that belongs to the family of nuclear receptors. Some studies have reported the protective effect of Pro12Ala variant of PPARγ2 gene in insulin resistance and metabolic deregulation, though other has reported variable result.

Aim:To study Pro12Ala polymorphism of PPARγ2 gene in relation to BMI & HbA1C in Type 2 Diabetes (T2D) subjects from Western India.

Materials & Method: Present study comprises of prospective 415 subjects that include 177 T2D patients & 238 non-diabetic subjects. T2D patients were divided in two groups according to the BMI. Group-I includes 57 subjects with BMI of ≤ 24.9 Kg/m2 and group-II includes 120 subjects with BMI of ≥ 25.0 Kg/m2. An institutional ethical committee approval and prior informed consent was obtained from all subjects. Anthropometric indices like BMI, Waist Hip Ratio and biochemical parameters like FBS, PPBS, HbA1C, Insulin and Lipid profile were carried out in every subject. Genotype study of all the cases were carried out for Pro12Ala (C34G) variation of PPARγ2 gene.

 Results: In the studied population, Pro/Pro (CC) genotype is predominantly observed in T2D patients as well as controls. Ala allele frequency was 10.08% in control subjects as compared with 10.73% in T2D patients. The mean HbA1C level of all T2D patients was 8.3% out of which 20.33% patients had Pro12Ala polymorphism and 79.67% patients were homozygous for 12Pro allele. On stratifying the data, mean HbA1C of T2D patients with 12Ala allele was 8.0% compared to 8.5% in patients without 12Ala allele (p >0.05).

Nonetheless, a significant decrease in mean HbA1C was observed in group-I T2D subjects as compared to group-II with Pro12Ala polymorphism (7.5% vs. 8.1%, p <0.03). In control subjects there was no significant effect of either polymorphism or BMI on HbA1C.

Conclusion: The frequency of PPARγ2 gene polymorphism (Pro12Ala) is nearly equal in T2D patients & control subjects of Western India. When this polymorphism is compared with BMI & HbA1C, a significant decrease in HbA1C level was observed in non-obese T2D patients (p <0.03). This protective effect of 12Ala allele seems to decrease in obese diabetic patients. It is likely that this protective effect of 12Ala allele is due to the alteration in transcriptional activity in adipocytes. It can be concluded from this study that 12Ala allele has a beneficial effect on glycation in non-obese T2D subjects.

Nothing to Disclose: AM, JJS, FS, MP, BD, NNS, PT, RV

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Gujarat Institute of Chemical Technology (GICT).Ahmedabad, Gujarat, India.