Sickle cell trait is not independently associated with susceptibility to end-stage renal disease in African Americans

Kidney Int. 2011 Dec;80(12):1339-43. doi: 10.1038/ki.2011.286. Epub 2011 Aug 17.

Abstract

Conflicting reports exist as to whether sickle cell trait is a risk factor for the progression of nephropathy. In order to determine whether African Americans with sickle cell trait are at increased risk for kidney disease, we assessed the genetic association between sickle cell trait and end-stage renal disease (ESRD). Hemoglobin S, non-muscle myosin heavy chain 9 (MYH9), and apolipoprotein L1 (APOL1) risk variants were genotyped in 3258 unrelated African Americans: 1085 with non-diabetic ESRD, 996 with type 2 diabetes-associated ESRD, and 1177 controls. Since APOL1 is strongly associated with ESRD in African Americans, interactions between APOL1 and MYH9 risk variants and hemoglobin S were assessed using case-only and case-control centered two-way logistic regression interaction analyses. The sickle cell trait genotype frequencies were 8.7% in non-diabetic ESRD, 7.1% in type 2 diabetes-ESRD, and 7.2% in controls. There was no age-, gender-, and admixture-adjusted significance for sickle cell trait association with non-diabetic ESRD (odds ratio 1.16); type 2 diabetes-ESRD (odds ratio 1.01); or all-cause ESRD (combined non-diabetic and type 2 diabetic-ESRD patients compared to the controls; odds ratio 1.05) in dominant models. In addition, no evidence of APOL1 or MYH9 interactions with sickle cell trait was detected. Hence, sickle cell trait is not associated with diabetic or non-diabetic ESRD in a large sample of African Americans.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Apolipoprotein L1
  • Apolipoproteins / genetics*
  • Black or African American / genetics*
  • Case-Control Studies
  • Diabetic Nephropathies / ethnology
  • Diabetic Nephropathies / genetics*
  • Disease Progression
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Hemoglobin, Sickle / genetics*
  • Humans
  • Kidney Failure, Chronic / ethnology
  • Kidney Failure, Chronic / genetics*
  • Lipoproteins, HDL / genetics*
  • Logistic Models
  • Male
  • Middle Aged
  • Molecular Motor Proteins / genetics*
  • Myosin Heavy Chains / genetics*
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Risk Assessment
  • Risk Factors
  • Sickle Cell Trait / ethnology
  • Sickle Cell Trait / genetics*
  • United States / epidemiology

Substances

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