Genetic polymorphism protects against albuminuria, nephropathy in T2DM

The substitution of proline-12 to alanine (Pro12Ala) in the proliferator-activated receptorγ2 gene (PPARγ2) appears to be protective against albuminuria and diabetic nephropathy (DN) in type 2 diabetes mellitus (T2DM) patients, a new study has found.

Researchers conducted a case-control study on 554 T2DM patients, of whom 313 (mean age, 60.8±9.9 years; 54.3 percent female) had normal urinary albumin levels; the remaining 241 (mean age, 62.6±9.5 years; 39.8 percent female) had albuminuria. Peripheral blood samples were drawn and subjected to real-time polymerase chain reaction-based genotyping assays for the assessment of Pro12Ala polymorphisms.

The allele frequency of Ala12 was only 4 percent. Almost all (92.6 percent; n=513) of the participants bore the Pro12Pro PPARγ2 genotype, while only 7.0 percent (n=39) showed the Pro12Ala polymorphism. Two participants (0.4 percent) carried the Ala12Ala phenotype.

All alanine carriers demonstrated significantly lower urinary albumin-to-creatinine ratio (15.0 vs 25.0 mg/g; p=0.001) and better renal function, as determined by the estimated glomerular filtration rate (81.8 vs 78.7 mL/min/1.73m²; p=0.05). Participants with the Pro12Pro PPARγ2 genotype were used as reference.

Notably, the prevalence of DN was significantly elevated among the Pro12Pro patients (44.8 percent vs 26.8 percent; p=0.025) relative to alanine carriers.

The primary findings were confirmed in multivariate logistic regression analysis, which found that alanine carriers were significantly protected from albuminuria (odds ratio [OR], 0.428, 95 percent confidence interval, 0.195–0.940; p=0.034). The male sex, retinopathy and the use of angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonist, on the other hand, were significant risk factors.