Apolipoprotein L1 gene variants associate with hypertension-attributed nephropathy and the rate of kidney function decline in African Americans

Kidney Int. 2013 Jan;83(1):114-20. doi: 10.1038/ki.2012.263. Epub 2012 Jul 25.

Abstract

Despite intensive antihypertensive therapy there was a high incidence of renal end points in participants of the African American Study of Kidney Disease and Hypertension (AASK) cohort. To better understand this, coding variants in the apolipoprotein L1 (APOL1) and the nonmuscle myosin heavy chain 9 (MYH9) genes were evaluated for an association with hypertension-attributed nephropathy and clinical outcomes in a case-control study. Clinical data and DNA were available for 675 AASK participant cases and 618 African American non-nephropathy control individuals. APOL1 G1 and G2, and MYH9 E1 variants along with 44 ancestry informative markers, were genotyped with allele frequency differences between cases and controls analyzed by logistic regression multivariable models adjusting for ancestry, age, and gender. In recessive models, APOL1 risk variants were significantly associated with kidney disease in all cases compared to controls with an odds ratio of 2.57. In AASK cases with more advanced disease, such as a baseline urine protein to creatinine ratio over 0.6 g/g or a serum creatinine over 3 mg/dl during follow-up, the association was strengthened with odds ratios of 6.29 and 4.61, respectively. APOL1 risk variants were consistently associated with renal disease progression across medication classes and blood pressure targets. Thus, kidney disease in AASK participants was strongly associated with APOL1 renal risk variants.

Publication types

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

MeSH terms

  • Adult
  • African Americans / ethnology*
  • African Americans / genetics*
  • Aged
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Apolipoprotein L1
  • Apolipoproteins / genetics*
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Case-Control Studies
  • Creatinine / blood
  • Female
  • Gene Frequency / genetics
  • Genetic Variation / genetics*
  • Glomerular Filtration Rate / drug effects
  • Glomerular Filtration Rate / physiology
  • Humans
  • Hypertension, Renal / drug therapy
  • Hypertension, Renal / ethnology*
  • Hypertension, Renal / genetics*
  • Kidney / physiopathology*
  • Lipoproteins, HDL / genetics*
  • Male
  • Middle Aged
  • Molecular Motor Proteins / genetics
  • Myosin Heavy Chains / genetics
  • Nephritis / drug therapy
  • Nephritis / ethnology*
  • Nephritis / genetics*
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

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

Supplementary concepts

  • Hypertensive Nephropathy