Polymorphisms in MYH9 are associated with diabetic nephropathy in European Americans

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

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

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

Substances

  • MYH9 protein, human
  • Molecular Motor Proteins
  • Myosin Heavy Chains