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Comparative Study
. 2012 Apr;27(4):1505-11.
doi: 10.1093/ndt/gfr522. Epub 2011 Oct 3.

Polymorphisms in MYH9 are associated with diabetic nephropathy in European Americans

Jessica N Cooke  1 , Meredith A Bostrom, Pamela J Hicks, Maggie C Y Ng, Jacklyn N Hellwege, Mary E Comeau, Jasmin Divers, Carl D Langefeld, Barry I Freedman, Donald W Bowden
Affiliations
Comparative Study

Polymorphisms in MYH9 are associated with diabetic nephropathy in European Americans

Jessica N Cooke et al. Nephrol Dial Transplant. 2012 Apr.

Abstract

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.

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Figures

Fig. 1.
Fig. 1.
Gene structure and linkage disequilibrium plot generated by 15 SNPs genotyped in European Americans. Inter-SNP D’-values are displayed on the plot.
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References

    1. U.S. Renal Data System. USRDS 2009 Annual Data Report. Atlas of chronic kidney Disease and End-Stage Renal Disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2009.
    1. Bowden DW. Genetics of kidney disease. Kidney Int Suppl. 2003;83:S8–S12. - PubMed
    1. O'Dea DF, Murphy SW, Hefferton D, et al. Higher risk for renal failure in first-degree relatives of white patients with end-stage renal disease: a population-based study. Am J Kidney Dis. 1998;32:794–801. - PubMed
    1. Spray BJ, Atassi NG, Tuttle AB, et al. Familial risk, age at onset, and cause of end-stage renal disease in white Americans. J Am Soc Nephrol. 1995;5:1806–1810. - PubMed
    1. Satko SG, Sedor JR, Iyengar SK, et al. Familial clustering of chronic kidney disease. Semin Dial. 2007;20:229–236. - PubMed

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