Barry I. Freedman

Donald W. Bowden

Janice P. Lea

Jason A. Bonomo

John Cijiang He

Mark D. Okusa

Pamela J. Hicks

Ying Fan

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; The reticulon 1 gene &lt;i&gt;(RTN1)&lt;/i&gt; encodes reticulons, endoplasmic reticulum stress proteins recently implicated in kidney disease progression. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt;&lt;i&gt;RTN1&lt;/i&gt; 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. &lt;i&gt;RTN1&lt;/i&gt; 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. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Three intronic &lt;i&gt;RTN1&lt;/i&gt; 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&lt;sup&gt;-4&lt;/sup&gt; (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&lt;sup&gt;-4&lt;/sup&gt;, OR 0.73) and rs12431381 (p = 7.5 × 10&lt;sup&gt;-4&lt;/sup&gt;, 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). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; These results suggest evidence of genetic association between common variants in &lt;i&gt;RTN1&lt;/i&gt; and ESKD in AAs and EAs.</jats:p

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American Journal of Nephrology

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

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

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