A genome-wide association study for diabetic nephropathy genes in African Americans

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...

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Veröffentlicht in:Kidney international Jg. 79; H. 5; S. 563 - 572
Hauptverfasser: McDonough, Caitrin W., Palmer, Nicholette D., Hicks, Pamela J., Roh, Bong H., An, S Sandy, Cooke, Jessica N., Hester, Jessica M., Wing, Maria R., Bostrom, Meredith A., Rudock, Megan E., Lewis, Joshua P., Talbert, Matthew E., Blevins, Rebecca A., Lu, Lingyi, Ng, Maggie C Y, Sale, Michele M., Divers, Jasmin, Langefeld, Carl D., Freedman, Barry I., Bowden, Donald W.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Basingstoke Elsevier Inc 01.03.2011
Nature Publishing Group
Elsevier Limited
Schlagworte:
Adult
Aged
Associated diseases and complications
Biological and medical sciences
Black or African American - genetics
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - genetics
Diabetes. Impaired glucose tolerance
Diabetic Nephropathies - genetics
diabetic nephropathy
end-stage renal disease
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
ethnic minority
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
human genetics
Humans
Kidney Failure, Chronic - genetics
Kidneys
Male
Medical sciences
Middle Aged
Nephrology. Urinary tract diseases
Polymorphism, Single Nucleotide
polymorphisms
Urinary system involvement in other diseases. Miscellaneous
human genetics
end-stage renal disease
ethnic minority
polymorphisms
diabetic nephropathy
Endocrinopathy
Kidney disease
Concomitant disease
Nephrology
Urinary system disease
Gene
Diabetes mellitus
Genetics
Diabetic nephropathy
Genome
Urology
African American
ISSN:0085-2538, 1523-1755, 1523-1755
Online-Zugang:Volltext
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Zusammenfassung: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.
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ISSN:0085-2538
1523-1755
1523-1755
DOI:10.1038/ki.2010.467