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

被引：10

作者：

Bonomo, Jason A. ^{[1
]}

Palmer, Nicholette D. ^{[1
]}

He, John Cijiang ^{[3
]}

Fan, Ying ^{[3
]}

Hicks, Pamela J. ^{[1
]}

Lea, Janice P. ^{[4
]}

Okusa, Mark D. ^{[5
]}

Bowden, Donald W. ^{[1
]}

Freedman, Barry I. ^{[2
]}

机构：

[1] Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA

[2] Wake Forest Sch Med, Nephrol Sect, Dept Internal Med, Winston Salem, NC 27157 USA

[3] Mt Sinai Sch Med, Dept Internal Med, Div Nephrol, New York, NY USA

[4] Emory Sch Med, Dept Internal Med, Div Renal Med, Atlanta, GA USA

[5] Univ Virginia, Sch Med, Dept Internal Med, Div Nephrol, Charlottesville, VA 22908 USA

来源：

AMERICAN JOURNAL OF NEPHROLOGY | 2015年 / 42卷 / 04期

基金：

美国国家卫生研究院;

关键词：

African Americans; Chronic kidney disease; Diabetes; Diabetic kidney disease; Genetics; Reticulon; 1; AFRICAN-AMERICANS; DIABETES-MELLITUS; NEPHROPATHY;

D O I：

10.1159/000441199

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Background: The reticulon 1 gene (RTN1) encodes reticulons, endoplasmic reticulum stress proteins recently implicated in kidney disease progression. Methods: 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. Results: 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 x 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 x 10(-4), OR 0.73) and rs12431381 (p = 7.5 x 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). Conclusions: These results suggest evidence of genetic association between common variants in RTN1 and ESKD in AAs and EAs. (C) 2015 S. Karger AG, Basel

引用

页码：259 / 264

页数：6

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