Abstract P165: Genetic Polymorphisms Linked to Diabetes With Chronic Renal Insufficiency

Abstract

Chronic kidney disease (CKD) has raised to a global health concern with huge economic burden and detrimental consequences for health. Among the risk factors, diabetes is a leading cause for CKD and renal failure. Multiple studies such as familial aggregation studies have provided evidence for a genetic component to the kidney disease. Heritability estimates of eGFRcrea are reported between 0.41 and 0.75 in individuals with the major CKD risk factors, hypertension and diabetes. However, precise genetic loci predicting CKD with or without diabetes are unknown. Here, we test the hypothesis that genetic polymorphisms are distinct between CKD patients with and without diabetes. We performed a genome-wide association studies using data from the Chronic Renal Insufficiency Cohort (CRIC) study to identify genetic various related to diabetes among CKD patients. CRIC Study is a United States multicenter, prospective study of racially and ethnically diverse patients with CKD. Clean genotype data from 970,342 genotyped or imputed single-nucleotide polymorphisms (SNPs) were available for 3,541 patients (1,953 males and 1,588 females) in CRIC study. Logistic regressions were carried out comparing distribution of SNPs among CKD patients with or without diabetes controlling for confounding factors of gender and race. Among all 3,541 CKD patients in CRIC, 1,724 CKD patients had Diabetes at baseline (Mean of Glycosylated hemoglobin =7.7%). We found that three genes, including KCNMB4 (rs767397, encoding calcium-activated potassium channel, subfamily M subunit beta 4), FOXA1 (rs911822, encoding a forkhead transcription factor) and SIMC1 (rs16831314, encoding SUMO-interacting motif containing protein 1), were putative risk genes for diabetes among CKD patients (P-value<5х10 -6 ). These results are the first demonstrating that distinct genetic polymorphisms present in CKD patients with diabetes, indicating that these genes may be used to assess the risk of CKD with diabetes and that proteins encoded by these genes may contribute to diabetic nephropathy.