Polymorphisms in MYH9 are associated with diabetic nephropathy in European Americans.

Cooke JN, Bostrom MA, Hicks PJ, Ng MC, Hellwege JN, Comeau ME, Divers J, Langefeld CD, Freedman BI, Bowden DW
Nephrol Dial Transplant. 2012 27 (4): 1505-11

PMID: 21968013 · PMCID: PMC3315672 · DOI:10.1093/ndt/gfr522

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.

MeSH Terms (17)

Case-Control Studies Cohort Studies Diabetes Complications Diabetes Mellitus, Type 2 Diabetic Nephropathies European Continental Ancestry Group Female Genetic Predisposition to Disease Genotype Humans Kidney Failure, Chronic Male Middle Aged Molecular Motor Proteins Myosin Heavy Chains Polymorphism, Single Nucleotide Prognosis

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