The non-muscle Myosin heavy chain 9 gene (MYH9) is not associated with lupus nephritis in African Americans

Am J Nephrol. 2010;32(1):66-72. doi: 10.1159/000314688. Epub 2010 Jun 7.

Abstract

Background: African Americans (AA) disproportionately develop lupus nephritis (LN) relative to European Americans and familial clustering supports causative genes. Since MYH9 underlies approximately 40% of end-stage renal disease (ESRD) in AA, we tested for genetic association with LN.

Methods: Seven MYH9 single nucleotide polymorphisms (SNPs) and the E1 risk haplotype were tested for association with LN in three cohorts of AA.

Results: A preliminary analysis revealed that the MYH9 E1 risk haplotype was associated with ESRD in 25 cases with presumed systemic lupus erythematosus (SLE)-associated ESRD, compared to 735 non-SLE controls (odds ratio 3.1; p = 0.010 recessive). Replication analyses were performed in 583 AA with SLE in the PROFILE cohort (318 with LN; 265 with SLE but without nephropathy) and 60 AA from the NIH (39 with LN; 21 with SLE but without nephropathy). Analysis of the NIH and larger PROFILE cohorts, as well as a combined analysis, did not support this association.

Conclusions: These results suggest that AA with ESRD and coincident SLE who were recruited from dialysis clinics more likely have kidney diseases in the MYH9-associated spectrum of focal segmental glomerulosclerosis. PROFILE and NIH participants, recruited from rheumatology practices, demonstrate that MYH9 does not contribute substantially to the development of LN in AA.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • African Americans / genetics*
  • African Americans / statistics & numerical data*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / ethnology
  • Haplotypes
  • Humans
  • Lupus Nephritis / ethnology*
  • Lupus Nephritis / genetics*
  • Male
  • Middle Aged
  • Molecular Motor Proteins / genetics*
  • Myosin Heavy Chains / genetics*
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Young Adult

Substances

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