Polymorphisms in MYH9 are associated with diabetic nephropathy in European Americans

被引：73

作者：

Cooke, Jessica N. ^{[1
,2
,3
]}

Bostrom, Meredith A. ^{[1
,3
,4
]}

Hicks, Pamela J. ^{[1
,3
,4
]}

Ng, Maggie C. Y. ^{[1
,3
,4
]}

Hellwege, Jacklyn N. ^{[1
,4
,5
]}

Comeau, Mary E. ^{[6
]}

Divers, Jasmin ^{[6
]}

Langefeld, Carl D. ^{[6
]}

Freedman, Barry I. ^{[7
]}

Bowden, Donald W. ^{[1
,3
,4
,8
]}

机构：

[1] Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA

[2] Wake Forest Sch Med, Program Mol Med & Translat Sci, Winston Salem, NC USA

[3] Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA

[4] Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA

[5] Wake Forest Sch Med, Program Mol Genet & Genom, Winston Salem, NC USA

[6] Wake Forest Sch Med, Dept Publ Hlth Sci, Winston Salem, NC USA

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

[8] Wake Forest Sch Med, Dept Internal Med, Endocrinol Sect, Winston Salem, NC USA

来源：

NEPHROLOGY DIALYSIS TRANSPLANTATION | 2012年 / 27卷 / 04期

基金：

美国国家卫生研究院;

关键词：

APOL1; diabetic nephropathy; end-stage renal disease; MYH9; type 2 diabetes mellitus; STAGE RENAL-DISEASE; FOCAL SEGMENTAL GLOMERULOSCLEROSIS; CHRONIC KIDNEY-DISEASE; 9 GENE MYH9; AFRICAN-AMERICANS; VARIANTS; RISK; APOL1; SUSCEPTIBILITY; MELLITUS;

D O I：

10.1093/ndt/gfr522

中图分类号：

R3 [基础医学]; R4 [临床医学];

学科分类号：

1001 ; 1002 ; 100602 ;

摘要：

Background. Polymorphisms in the non-muscle myosin IIA gene (MYH9) are associated with focal segmental glomerulosclerosis (FSGS) and non-diabetic end-stage renal disease (ESRD) in African Americans and FSGS in European Americans. We tested for association of single nucleotide polymorphisms (SNPs) in MYH9 with T2DM-ESRD in European Americans; additionally, three APOL1 gene variants were evaluated. Methods. Fifteen MYH9 SNPs and two APOL1 SNPs plus a 6-bp deletion were genotyped in 1963 European Americans, 536 cases with T2DM-ESRD and 1427 non-nephropathy controls (467 with T2DM and 960 without diabetes). Results. Comparing T2DM-ESRD cases with the 467 T2DM non-nephropathy controls, single variant associations trending toward significance were detected with SNPs rs4821480, rs2032487 and rs4281481 comprising part of the major MYH9 E1 risk haplotype [P-values 0.053-0.055 recessive, odds ratio (OR) 6.08-6.14]. Comparing T2DM-ESRD cases to all 1427 non-nephropathy controls, we confirmed evidence of association in these three SNPs as well as in the fourth E1 SNP (rs3752462) (P-values 0.017-0.035, OR 1.41-3.72). APOL1 G1/G2 nephropathy risk variants were rare in individuals of European American heritage, present in 0.28% of chromosomes in T2DM-ESRD cases and 0.32% of controls. Conclusions. MYH9 SNPs rs4821480, rs2032487, rs4281481 and rs3752462 are associated with T2DM-ESRD susceptibility in European Americans. The APOL1 risk variants are not present at appreciable frequency in this cohort with T2DM-ESRD. Therefore, polymorphisms in MYH9 appear to influence nephropathy risk in this sample.

引用

页码：1505 / 1511

页数：7

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