The association of genetic variants of type 2 diabetes with kidney function

Type 2 diabetes is highly prevalent and is the major cause of progressive chronic kidney disease in American Indians. Genome wide association studies identified several loci associated with diabetes but their impact on susceptibility to diabetic complications is unknown. To measure this we studied the association of 18 type 2 diabetes genome wide association single nucleotide polymorphisms (SNPs) with the estimated glomerular filtration rate (eGFR) (MDRD equation) and urine albumin to creatinine ratio in 6,958 individuals in the Strong Heart Study family and cohort participants. Center specific residuals of eGFR and the log urine albumin to creatinine ratio, obtained from linear regression models adjusted for age, sex and body mass index, were regressed onto SNP dosage using variance component in family data and linear regression models in unrelated individuals. Estimates were then combined across centers. Four diabetic loci were associated with eGFR and one locus with the urine albumin to creatinine ratio. A SNP in the WFS1 gene (rs10010131) was associated with higher eGFR in younger individuals and with increased albuminuria. The SNPs of the FTO, KCNJ11 and TCF7L2 genes were associated with lower eGFR, not albuminuria, and were not significant in prospective analyses. Our findings suggest a shared genetic risk for type 2 diabetes, its kidney complications, and a potential role for WFS1 in early onset diabetic nephropathy in American Indian populations.