T2DM/CKD genetic risk scores and the progression of diabetic kidney disease in T2DM subjects

Abstract

Abstract This study explored the predictive value of genetic risk scores (GRS) for diabetic kidney disease (DKD) progression, Major Cardiovascular Events (MCVE), and All-Cause Mortality (ACM) in type 2 diabetes mellitus (T2DM) patients. We assessed 30 T2DM and CKD GWAS-derived single nucleotide polymorphisms (SNPs) in 400 Central European patients. Our analysis showed significant correlations between age, diabetes duration, diastolic blood pressure, total cholesterol, and eGFR with DKD progression (P < 0.05). No individual SNP strongly correlated with DKD progression, although CERS2 and SHROOM3 were near significance. WSF1 was associated with MCVE (P = 0.029), and CANCAS1, CERS2, and C9 were linked to ACM (P < 0.02). GRS did not surpass traditional clinical factors in predicting DKD, MCVE, or ACM. The model combining genetic and clinical factors only slightly improved the area under the curve (AUC) compared to the clinical model alone of 0.582 (95% CI 0.487–0.676) and 0.645 (95% CI 0.556–0.735), respectively, but this was not statistically significant (P = 0.06). Our findings underscore the complexity of genetic predictors in DKD progression and their interaction with clinical factors. Despite the potential of personalized medicine using genetic markers, our results suggest that conventional clinical factors are still crucial in predicting DKD in the Czech T2DM population. GWAS-derived GRSs did not show enhanced predictive capacity over standard clinical factors in this group.