Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis

Genes Immun. 2012 Apr;13(3):232-8. doi: 10.1038/gene.2011.82. Epub 2011 Dec 22.

Abstract

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and organ damage. Lupus nephritis (LN) is one of the most severe manifestations of SLE. Multiple studies reported associations between renal diseases and variants in the non-muscle myosin heavy chain 9 (MYH9) and the neighboring apolipoprotein L 1 (APOL1) genes. We evaluated 167 variants spanning MYH9 for association with LN in a multiethnic sample. The two previously identified risk variants in APOL1 were also tested for association with LN in European-Americans (EAs) (N = 579) and African-Americans (AAs) (N = 407). Multiple peaks of association exceeding a Bonferroni corrected P-value of P < 2.03 × 10(-3) were observed between LN and MYH9 in EAs (N = 4620), with the most pronounced association at rs2157257 (P = 4.7 × 10(-4), odds ratio (OR) = 1.205). A modest effect with MYH9 was also detected in Gullah (rs8136069, P = 0.0019, OR = 2.304). No association between LN and MYH9 was found in AAs, Asians, Amerindians or Hispanics. This study provides the first investigation of MYH9 in LN in non-Africans and of APOL1 in LN in any population, and presents novel insight into the potential role of MYH9 in LN in EAs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • African Americans / genetics*
  • Apolipoprotein L1
  • Apolipoproteins / genetics*
  • Genetic Predisposition to Disease
  • Humans
  • Linkage Disequilibrium
  • Lipoproteins, HDL / genetics*
  • Lupus Nephritis / ethnology*
  • Lupus Nephritis / genetics*
  • Molecular Motor Proteins / genetics*
  • Myosin Heavy Chains / genetics*
  • Polymorphism, Single Nucleotide
  • Whites / genetics

Substances

  • APOL1 protein, human
  • Apolipoprotein L1
  • Apolipoproteins
  • Lipoproteins, HDL
  • MYH9 protein, human
  • Molecular Motor Proteins
  • Myosin Heavy Chains

Grant support