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Am J Kidney Dis. 2012 Feb;59(2):210-21. doi: 10.1053/j.ajkd.2011.09.020. Epub 2011 Nov 25.

Genetic association and gene-gene interaction analyses in African American dialysis patients with nondiabetic nephropathy.

Author information

1
Wake Forest School of Medicine, Winston-Salem, NC, USA.

Abstract

BACKGROUND:

African Americans have increased susceptibility to nondiabetic nephropathy relative to European Americans.

STUDY DESIGN:

Follow-up of a pooled genome-wide association study (GWAS) in African American dialysis patients with nondiabetic nephropathy; novel gene-gene interaction analyses.

SETTING & PARTICIPANTS:

Wake Forest sample: 962 African American nondiabetic nephropathy cases, 931 non-nephropathy controls. Replication sample: 668 Family Investigation of Nephropathy and Diabetes (FIND) African American nondiabetic nephropathy cases, 804 non-nephropathy controls.

PREDICTORS:

Individual genotyping of top 1,420 pooled GWAS-associated single-nucleotide polymorphisms (SNPs) and 54 SNPs in 6 nephropathy susceptibility genes.

OUTCOMES:

APOL1 genetic association and additional candidate susceptibility loci interacting with or independently from APOL1.

RESULTS:

The strongest GWAS associations included 2 noncoding APOL1 SNPs, rs2239785 (OR, 0.33; dominant; P = 5.9 × 10(-24)) and rs136148 (OR, 0.54; additive; P = 1.1 × 10(-7)) with replication in FIND (P = 5.0 × 10(-21) and 1.9 × 10(-05), respectively). rs2239785 remained associated significantly after controlling for the APOL1 G1 and G2 coding variants. Additional top hits included a CFH SNP (OR from meta-analysis in the 3,367 African American cases and controls, 0.81; additive; P = 6.8 × 10(-4)). The 1,420 SNPs were tested for interaction with APOL1 G1 and G2 variants. Several interactive SNPs were detected; the most significant was rs16854341 in the podocin gene (NPHS2; P = 0.0001).

LIMITATIONS:

Nonpooled GWASs have not been performed in African American patients with nondiabetic nephropathy.

CONCLUSIONS:

This follow-up of a pooled GWAS provides additional and independent evidence that APOL1 variants contribute to nondiabetic nephropathy in African Americans and identified additional associated and interactive nondiabetic nephropathy susceptibility genes.

PMID:
22119407
PMCID:
PMC3259209
DOI:
10.1053/j.ajkd.2011.09.020
[Indexed for MEDLINE]
Free PMC Article

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