Polymorphisms in the non-muscle myosin heavy chain gene (MYH9) are associated with lower glomerular filtration rate in mixed ancestry diabetic subjects from South Africa

PLoS One. 2012;7(12):e52529. doi: 10.1371/journal.pone.0052529. Epub 2012 Dec 20.

Abstract

Objective: Though single nucleotide polymorphisms (SNPs) in the non-muscle myosin gene (MYH9) have been reported to explain most of the excess risk of nondiabetic chronic kidney disease (CKD), in African-Americans, some studies have also shown associations with diabetic end-stage renal disease. We investigated the association of MYH9 SNPs with renal traits in a mixed-ancestry South African population prone to diabetes.

Research design and methods: Three SNPs known to be associated with CKD (rs4821480, rs5756152 and rs12107) were genotyped using Taqman assay in 716 adults (198 with diabetes) from the Bellville-South community, Cape Town. Glomerular filtration rate was estimated (eGFR) and urinary albumin/creatinine ratio (ACR) assessed. Multivariable regressions were used to relate the SNPs with renal traits.

Results: Mean age was 53.6 years, with the expected differences observed in characteristics by diabetic status. Significant associations were found between rs575152 and serum creatinine, and eGFR in the total population, and in diabetic participants (all p≤0.003), but not in non-diabetics (all p≥0.16), with significant interactions by diabetes status (interaction-p≤0.009). The association with ACR was borderline in diabetic participants (p = 0.05) and non-significant in non-diabetics (p = 0.85), with significant interaction (interaction p = 0.02). rs12107 was associated with fasting-, 2-hour glucose and HbA1c in diabetic participants only (interaction-p≤0.003), but not with renal traits.

Conclusion: MYH9 SNPs were associated with renal traits only in diabetic participants in this population. Our findings and other studies suggest that MYH9 may have a broader genetic risk effect on kidney diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albuminuria / complications
  • Albuminuria / genetics
  • Albuminuria / physiopathology
  • Confidence Intervals
  • Diabetes Mellitus / genetics*
  • Diabetes Mellitus / physiopathology*
  • Female
  • Gene Frequency / genetics
  • Genealogy and Heraldry*
  • Genetic Predisposition to Disease*
  • Glomerular Filtration Rate / genetics*
  • Humans
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney / physiopathology
  • Linear Models
  • Male
  • Middle Aged
  • Molecular Motor Proteins / genetics*
  • Myosin Heavy Chains / genetics*
  • Odds Ratio
  • Polymorphism, Single Nucleotide / genetics*
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / genetics
  • Renal Insufficiency, Chronic / physiopathology
  • South Africa

Substances

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

Grants and funding

This research was supported by a grant from the University Research Fund of the Cape Peninsula University of Technology, South Africa. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.