Multi-variant genotyping identifies association of TRPC6 rs36111323 with diabetic kidney disease in a South Indian...

Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease and end-stage kidney failure worldwide. Genetic factors contribute to inter-individual and population-specific susceptibility to DKD. Data from South Indian populations are limited, highlighting the need for region-specific genetic association studies in DKD.

This case-control study included 125 South Indian individuals: 60 patients with diabetes and proteinuria (DKD), 34 patients with diabetes without kidney disease, and 31 healthy controls. Genomic DNA was isolated and nine variants were genotyped using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). Variant frequencies were compared among groups. In-silico pathogenicity prediction tools and Odds ratio (OR) with 95% confidence intervals (CIs) were estimated using multivariable logistic regression analyses were used to assess the association between genetic variants and DKD risk. Data visualization was performed using R statistical software. Among the nine variants analyzed, the TRPC6 rs36111323 (G > A; p.A404V) was independently associated with DKD (OR = 2.76; 95% CI = 1.04-7.34; p = 0.0418). This variant was more frequent in patients with DKD compared with diabetic patients without nephropathy and healthy controls. Pathogenicity prediction analyses supported a potentially deleterious effect of the variant.

The TRPC6 rs36111323 variant appears to be associated with increased susceptibility to diabetic kidney disease in a South Indian population, suggesting a population-specific genetic risk factor. Validation in larger cohorts and functional studies is warranted to clarify its role and potential application in precision nephrology.