title: A genome-wide association study for diabetic nephropathy genes in African Americans.
abstract: A genome-wide association study was performed using the Affymetrix 6.0 chip to identify genes associated with diabetic nephropathy in African Americans. Association analysis was performed adjusting for admixture in 965 type 2 diabetic African American patients with end-stage renal disease (ESRD) and in 1029 African Americans without type 2 diabetes or kidney disease as controls. The top 724 single nucleotide polymorphisms (SNPs) with evidence of association to diabetic nephropathy were then genotyped in a replication sample of an additional 709 type 2 diabetes-ESRD patients and 690 controls. SNPs with evidence of association in both the original and replication studies were tested in additional African American cohorts consisting of 1246 patients with type 2 diabetes without kidney disease and 1216 with non-diabetic ESRD to differentiate candidate loci for type 2 diabetes-ESRD, type 2 diabetes, and/or all-cause ESRD. Twenty-five SNPs were significantly associated with type 2 diabetes-ESRD in the genome-wide association and initial replication. Although genome-wide significance with type 2 diabetes was not found for any of these 25 SNPs, several genes, including RPS12, LIMK2, and SFI1 are strong candidates for diabetic nephropathy. A combined analysis of all 2890 patients with ESRD showed significant association SNPs in LIMK2 and SFI1 suggesting that they also contribute to all-cause ESRD. Thus, our results suggest that multiple loci underlie susceptibility to kidney disease in African Americans with type 2 diabetes and some may also contribute to all-cause ESRD.
authors.affiliation: Program in Molecular Medicine and Translational Science, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: Caitrin W
authors.initials: CW
authors.lastname: McDonough
authors.forename: Nicholette D
authors.initials: ND
authors.lastname: Palmer
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Hicks
authors.forename: Bong H
authors.initials: BH
authors.lastname: Roh
authors.forename: S Sandy
authors.initials: SS
authors.lastname: An
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Cooke
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Hester
authors.forename: Maria R
authors.initials: MR
authors.lastname: Wing
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Bostrom
authors.forename: Megan E
authors.initials: ME
authors.lastname: Rudock
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Lewis
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Talbert
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Blevins
authors.forename: Lingyi
authors.initials: L
authors.lastname: Lu
authors.forename: Maggie C Y
authors.initials: MC
authors.lastname: Ng
authors.forename: Michele M
authors.initials: MM
authors.lastname: Sale
authors.forename: Jasmin
authors.initials: J
authors.lastname: Divers
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide