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Association Analysis of the Reticulon 1 Gene in End-Stage Kidney Disease.


ABSTRACT: The reticulon 1 gene (RTN1) encodes reticulons, endoplasmic reticulum stress proteins recently implicated in kidney disease progression.RTN1 single nucleotide polymorphisms (SNPs) were tested for association with type 2 diabetes (T2D)-associated end-stage kidney disease (ESKD) in African Americans (AAs) and European Americans (EAs), and AAs with non-diabetic ESKD. RTN1 SNPs that were associated with T2D-ESKD in AA cases compared to non-nephropathy controls were identified from a discovery genome-wide association study (n=1,797), then tested for replication in 1,847 additional AA T2D-ESKD cases and controls.Three intronic RTN1 variants were nominally associated with T2D-ESKD in both discovery and replication analyses: rs1952034, rs12431381 and rs12434215 (additive models); combined T2D-ESKD (discovery+replication) p values were 0.015-3.0×10(-4) (ORs 0.67-0.77; minor alleles protective). In addition, rs12434215 was weakly associated with T2D-ESKD in 557 EA T2D-ESKD cases contrasted with 753 EA non-nephropathy controls (p=0.019; OR 0.69, dominant model). Nominal association extended to non-diabetic causes of ESKD in 1,459 additional AA cases (rs12431381 and rs12434215 p values 0.014-0.015; OR 0.77). An all-cause ESKD association analysis contrasted the 3,594 AA ESKD cases with 1,489 AA non-nephropathy controls and detected association with rs12434215 (p=6.7×10(-4), OR 0.73) and rs12431381 (p=7.5×10(-4), OR 0.75) in dominant models. Of the 3 SNPs, only rs12434215 was weakly associated with T2D per se when contrasting T2D non-nephropathy cases with non-diabetic controls (additive model p=0.032 AAs; p=0.048 EAs).These results suggest evidence of genetic association between common variants in RTN1 and ESKD in AAs and EAs.

SUBMITTER: Bonomo JA 

PROVIDER: S-EPMC4651726 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Association Analysis of the Reticulon 1 Gene in End-Stage Kidney Disease.

Bonomo Jason A JA   Palmer Nicholette D ND   He John Cijiang JC   Fan Ying Y   Hicks Pamela J PJ   Lea Janice P JP   Okusa Mark D MD   Bowden Donald W DW   Freedman Barry I BI  

American journal of nephrology 20151024 4


<h4>Background</h4>The reticulon 1 gene (RTN1) encodes reticulons, endoplasmic reticulum stress proteins recently implicated in kidney disease progression.<h4>Methods</h4>RTN1 single nucleotide polymorphisms (SNPs) were tested for association with type 2 diabetes (T2D)-associated end-stage kidney disease (ESKD) in African Americans (AAs) and European Americans (EAs), and AAs with non-diabetic ESKD. RTN1 SNPs that were associated with T2D-ESKD in AA cases compared to non-nephropathy controls were  ...[more]

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