Peroxisome proliferator activated receptor γ2 gene Pro12Ala gene polymorphism in type 2 diabetes and its relationship with diabetic nephropathy.

BACKGROUND

Despite intensive research, a genetic background of type 2 diabetes is still unknown as are causes of differences in the clinical course of the disease. This supports the hypothesis for factors of genetic susceptibility (or protection) to diabetic nephropathy. This study aimed to examine the association between Pro12Ala polymorphism in the PPARgamma2 gene with both type 2 diabetes and the development of diabetic nephropathy.

METHODS

The study included seventy subjects classified into three groups: healthy control group (20), diabetics without nephropathy (25), and diabetics with nephropathy (25). All members of the study were subjected to the following laboratory investigations: fasting glucose and insulin with calculation of insulin resistance by HOMA IR, HbA1c, urea, creatinine and calculation of creatinine clearance, lipid profile, urinary protein and/or microalbumin. Determination of Pro12Ala polymorphism in PPARgamma2 gene was done by PCR/RFLP.

RESULTS

As regards PPARgamma2 Pro12Ala gene polymorphism, the Pro/Pro genotype was the most common in diabetic patients as well as in controls followed by Pro/Ala genotype and Ala/Ala genotypes was the least common one. The genotype distribution of the PPARgamma2 polymorphism was significantly different in diabetic patients compared to controls and in diabetics with nephropathy compared to those without nephropathy (p < 0.05). The allelic frequency of proline (Pro) was significantly higher in diabetic patients than controls (p < 0.001) and also significantly higher in diabetics with nephropathy than without nephropathy (p < 0.05). The odds ratio (OR) of having diabetes for Pro allele carriers was 8 compared with noncarriers (95% CI: 2.66 - 23.98).

CONCLUSIONS

Our results support the association between the Pro allele of PPARgamma2 gene and both development of type 2 diabetes and diabetic nephropathy.