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

Michael S. Lipkowitz, Barry I. Freedman, Carl D. Langefeld, Mary E. Comeau, Donald W. Bowden, W. H.Linda Kao, Brad C. Astor, Erwin P. Bottinger, Sudha K. Iyengar, Paul E. Klotman, Richard G. Freedman, Weijia Zhang, Rulan S. Parekh, Michael J. Choi, George W. Nelson, Cheryl A. Winkler, Jeffrey B. Kopp

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)114-120
Number of pages7
JournalKidney international
Volume83
Issue number1
DOIs
StatePublished - Jan 2013

Keywords

  • AASK (African American Study of Kidney Disease and Hypertension)
  • APOL1
  • chronic kidney disease
  • ethnic minority
  • human genetics
  • hypertension

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Apolipoprotein L1 gene variants associate with hypertension-attributed nephropathy and the rate of kidney function decline in African Americans'. Together they form a unique fingerprint.

Cite this