MYH9 and APOL1 are both associated with sickle cell disease nephropathy.

Published

Journal Article

Renal failure occurs in 5-18% of sickle cell disease (SCD) patients and is associated with early mortality. At-risk SCD patients cannot be identified prior to the appearance of proteinuria and the pathobiology is not well understood. The myosin, heavy chain 9, non-muscle (MYH9) and apolipoprotein L1 (APOL1) genes have been associated with risk for focal segmental glomerulosclerosis and end-stage renal disease in African Americans. We genotyped 26 single nucleotide polymorphisms (SNPs) in MYH9 and 2 SNPs in APOL1 (representing the G1 and G2 tags) in 521 unrelated adult (18-83 years) SCD patients screened for proteinuria. Using logistic regression, SNPs were evaluated for association with proteinuria. Seven SNPs in MYH9 and one in APOL1 remained significantly associated with proteinuria after multiple testing correction (P < 0·0025). An MYH9 risk haplotype (P = 0·001) and the APOL1 G1/G2 recessive model (P < 0·0001) were strongly associated with proteinuria, even when accounting for the other. Glomerular filtration rate was negatively correlated with proteinuria (P < 0·0001), and was significantly predicted by an interaction between MYH9 and APOL1 in age-adjusted analyses. Our data provide insight into the pathobiology of renal dysfunction in SCD, suggesting that MYH9 and APOL1 are both associated with risk.

Full Text

Duke Authors

Cited Authors

  • Ashley-Koch, AE; Okocha, EC; Garrett, ME; Soldano, K; De Castro, LM; Jonassaint, JC; Orringer, EP; Eckman, JR; Telen, MJ

Published Date

  • November 2011

Published In

Volume / Issue

  • 155 / 3

Start / End Page

  • 386 - 394

PubMed ID

  • 21910715

Pubmed Central ID

  • 21910715

Electronic International Standard Serial Number (EISSN)

  • 1365-2141

International Standard Serial Number (ISSN)

  • 0007-1048

Digital Object Identifier (DOI)

  • 10.1111/j.1365-2141.2011.08832.x

Language

  • eng