A genome scan for diabetic nephropathy in African Americans

Background. There is substantial evidence for a genetic contribution to diabetic nephropathy susceptibility in the African American population, but little is known about location or identity of susceptibility genes. Methods. DNA samples were collected from 206 type 2 diabetes (T2DM) and end-stage renal disease (ESRD)/nephropathy-affected sib pairs from 166 African American families (355 affected individuals). A genome scan was performed and data analyzed using nonparametric linkage regression (NPLR) analysis and ordered subsets analysis (OSA) methods. Results. In initial NPLR analyses no logarithm of odds (LOD) scores >2.0 were observed. Four loci had LOD scores greater than or equal to1.0, with LOD=1.43 at 29 cM on chromosome 7p the highest. NPLR analyses of multilocus interactions detected 6 loci (7p, 12p, 14q, 16p, 18q, and 21q) with LOD scores 1.15 to 1.63. NPLR analyses evaluating phenotypic interactions revealed multiple locations with evidence (P<0.05) for interactions with age-at-onset of ESRD (9 loci), duration of diabetes before onset of ESRD (19 loci), and age-at-onset of diabetes (14 loci). Several loci identified by NPLR analyses were also identified using OSA. OSA revealed evidence for a nephropathy locus at 135 cM on chromosome 3 in an estimated 29% of the families (LOD=4.55 in the optimal subset). Additional linkage evidence, LOD=3.59, was observed on chromosome 7p (37% of the families, longer duration of diabetes prior to diagnosis of ESRD), and 18q (max. LOD=3.72; 64% of the families, early diabetes diagnosis). The 7p linkage has been observed in a recent genome scan of African American type 2 diabetes. Conclusion. This first genome scan of diabetic nephropathy in African Americans reveals evidence for susceptibility loci on chromosomes 3q, 7p, and 18q. The 7p locus may represent a type 2 diabetes susceptibility locus.