Unknown

Dataset Information

0

Relevance of the ACTN4 gene in African-Americans with non-diabetic end-stage renal disease.


ABSTRACT: African-Americans (AAs) are predisposed to non-diabetic (non-DM) end-stage renal disease (ESRD), and studies have shown a genetic component to this risk. Rare mutations in ACTN4 (?-actinin-4), an actin-binding protein expressed in podocytes, cause familial focal segmental glomerulosclerosis.We assessed the contribution of coding variants in ACTN4 to non-DM ESRD risk in AAs. Nineteen exons, 2,800 bases of the promoter and 392 bases of the 3' untranslated region of ACTN4 were sequenced in 96 AA non-DM ESRD cases and 96 non-nephropathy controls (384 chromosomes). Sixty-seven single-nucleotide polymorphisms (SNPs) including 51 novel SNPs were identified. The SNPs comprised 33 intronic, 21 promoter, 12 exonic, and one 3' variant. Sixty-two of the SNPs were genotyped in 296 AA non-DM ESRD cases and 358 non-nephropathy controls.One SNP, rs10404257, was associated with non-DM ESRD (p < 1.0E-4, odds ratio, OR = 0.76; confidence interval, CI = 0.59-0.98; additive model). Forty-seven SNPs had minor allele frequencies <5%. These SNPs were segregated into risk and protective SNPs, and each category was collapsed into a single marker, designated by the presence or absence of any rare allele. The presence of any rare allele at a risk SNP was significantly associated with non-DM ESRD (p = 0.001, dominant model). The SNPs with the strongest evidence for association (n = 20) were genotyped in an independent set of 467 non-DM ESRD cases and 279 controls. Although rs10404257 was not associated in this replication sample, when the samples were combined, rs10404257 was modestly associated (p = 0.032, OR = 0.78, CI = 0.63-0.98; dominant model). SNPs were tested for interaction with markers in the APOL1 gene, previously associated with non-DM ESRD in AAs, and rs10404257 was modestly associated (p = 0.0261, additive model).This detailed evaluation of ACTN4 variation revealed limited evidence of association with non-DM ESRD in AAs.

SUBMITTER: Bostrom MA 

PROVIDER: S-EPMC3510331 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

altmetric image

Publications

Relevance of the ACTN4 gene in African-Americans with non-diabetic end-stage renal disease.

Bostrom Meredith A MA   Perlegas Peter P   Lu Lingyi L   Hicks Pamela J PJ   Hawkins Greg G   Ng Maggie C Y MC   Langefeld Carl D CD   Freedman Barry I BI   Bowden Donald W DW  

American journal of nephrology 20120904 3


<h4>Background</h4>African-Americans (AAs) are predisposed to non-diabetic (non-DM) end-stage renal disease (ESRD), and studies have shown a genetic component to this risk. Rare mutations in ACTN4 (α-actinin-4), an actin-binding protein expressed in podocytes, cause familial focal segmental glomerulosclerosis.<h4>Methods</h4>We assessed the contribution of coding variants in ACTN4 to non-DM ESRD risk in AAs. Nineteen exons, 2,800 bases of the promoter and 392 bases of the 3' untranslated region  ...[more]

Similar Datasets

| S-EPMC2786015 | biostudies-literature
| S-EPMC2614692 | biostudies-literature
| S-EPMC2850615 | biostudies-literature
| S-EPMC2661602 | biostudies-literature
| S-EPMC4002759 | biostudies-literature
| S-EPMC4081633 | biostudies-literature
| S-EPMC7220318 | biostudies-literature
| S-EPMC2698223 | biostudies-literature
| S-EPMC3280424 | biostudies-literature
| S-EPMC4906013 | biostudies-literature