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Author Notes:

Correspondence: Allison Ashley-Koch, Ph.D., Center for Human Genetics, Duke University Medical Center, Box 3445, 905 S. LaSalle Street, Durham, NC 27710, allison.ashleykoch@duke.edu, Phone: (919) 684-1805.

AAK designed the research study, contributed essential reagents, and wrote the paper; ECO performed the research and wrote the paper; MEG analysed the data and wrote the paper; KS performed the research and wrote the paper; LMD performed the research and contributed essential reagents; JCJ performed the research; EPO and JRE designed the study and contributed essential reagents; MJT designed the research study, contributed essential reagents, and wrote the paper.

Disclosures: None.

Subjects:

Research Funding:

This work was funded in part by RO1 HL079915 from the National Heart, Lung and Blood Institute, USA.

ECO received support from R90/T90 HG004150.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Hematology
  • sickle cell disease
  • nephropathy
  • genetics association
  • genetic modifier
  • proteinuria
  • FOCAL SEGMENTAL GLOMERULOSCLEROSIS
  • ANGIOTENSIN-CONVERTING ENZYME
  • STAGE RENAL-DISEASE
  • AFRICAN-AMERICANS
  • KIDNEY-DISEASE
  • LINKAGE PHASE
  • PREVALENCE
  • RISK
  • PODOCYTES
  • ANEMIA

MYH9 and APOL1 are both associated with sickle cell disease nephropathy

Tools:

Journal Title:

British Journal of Haematology

Volume:

Volume 155, Number 3

Publisher:

, Pages 386-394

Type of Work:

Article | Post-print: After Peer Review

Abstract:

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 (18-83years) 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 APOL1G1/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.

Copyright information:

© 2011 Blackwell Publishing Ltd.

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