The protective effect of the Pro12Ala polymorphism of peroxisome proliferator-activated receptor γ (PPARγ) isoform 2 in progression to diabetes in a Pakistani cohort

Diabetes is a serious health issue in Pakistan with 6.9 million cases of diabetes and 87,548 deaths due to diabetes in Pakistan in 2014. Peroxisome proliferators-activated receptors are transcription factors, regulating several physiological processes The aims of the current study were to determine the prevalence of Pro12Ala polymorphism (C>G) of PPAR-y iso-form 2 gene and analyze its effect on selected anthropometric and biochemical parameters in a Pakistani cohort. We collected 926 samples, 500 healthy controls (fasting blood sugar < 99 mg/dL, random blood sugar < 126 mg/dL) and 426 cases with diabetes (fasting blood sugar > 99 mg/dL, random blood sugar > 126 mg/dL). The genotyping was done and serum biochemical parameters were determined. The results showed allelic frequency C = 0.716 and G = 0.284 in controls and C = 0.766 and G = 0.234 in diabetic cases; whereas, genotypic frequency was CC = 52.2%, CG = 38.8%, and GG = 9% in controls and CC = 57.7%, CG = 37.8%, GG = 4.5% in cases. The association of Pro12Ala polymorphism under additive, dominant, and recessive models was checked (additive OR 0.58, CI 0.44–0.77, p value 0.0002, dominant OR 0.60, CI 0.44–0.82, p value 0.001, recessive OR 0.36, CI 0.15–0.86, p value 0.016). The result showed that the polymorphism is significantly associated with the decreased risk of diabetes in the Pakistani study subjects under additive models. The variant showed an association with weight, BMI, blood glucose, TC, HDL-C, insulin, and HOMA-IR. In conclusion, the presence of minor allele lowers the risk of diabetes and the effect may involve modulating serum glucose and lipid levels.