Apolipoprotein L1 Variants and Blood Pressure Traits in African Americans

J Am Coll Cardiol. 2017 Mar 28;69(12):1564-1574. doi: 10.1016/j.jacc.2017.01.040.

Abstract

Background: African Americans (AA) are disproportionately affected by hypertension-related health disparities. Apolipoprotein L1 (APOL1) risk variants are associated with kidney disease in hypertensive AAs.

Objectives: This study assessed the APOL1 risk alleles' association with blood pressure traits in AAs.

Methods: The discovery cohort included 5,204 AA participants from Mount Sinai's BioMe biobank. Replication cohorts included additional BioMe (n = 1,623), Vanderbilt BioVU (n = 1,809), and Northwestern NUgene (n = 567) AA biobank participants. Single nucleotide polymorphisms determining APOL1 G1 and G2 risk alleles were genotyped in BioMe and imputed in BioVU/NUgene participants. APOL1 risk alleles' association with blood pressure-related traits was tested in the discovery cohort, a meta-analysis of replication cohorts, and a combined meta-analysis under recessive and additive models after adjusting for age, sex, body mass index, and estimated glomerular filtration rate.

Results: There were 14% to 16% of APOL1 variant allele homozygotes (2 copies of G1/G2) across cohorts. APOL1 risk alleles were associated under an additive model with systolic blood pressure (SBP) and age at diagnosis of hypertension, which was 2 to 5 years younger in the APOL1 variant allele homozygotes (Cox proportional hazards analysis, p value for combined meta-analysis [pcom] = 1.9 × 10-5). APOL1 risk alleles were associated with overall SBP (pcom = 7.0 × 10-8) and diastolic blood pressure (pcom = 2.8 × 10-4). After adjustment for all covariates, those in the 20- to 29-year age range showed an increase in SBP of 0.94 ± 0.44 mm Hg (pcom = 0.01) per risk variant copy. APOL1-associated estimated glomerular filtration rate decline was observed starting a decade later in life in the 30- to 39-year age range.

Conclusions: APOL1 risk alleles are associated with higher SBP and earlier hypertension diagnoses in young AAs; this relationship appears to follow an additive model.

Keywords: APOL1; allele; estimated glomerular filtration rate; genetic association studies; kidney disease.

MeSH terms

  • Adult
  • African Americans / genetics
  • Aged
  • Apolipoprotein L1
  • Apolipoproteins / genetics*
  • Blood Pressure / genetics*
  • Cohort Studies
  • Female
  • Humans
  • Hypertension / ethnology
  • Hypertension / genetics*
  • Lipoproteins, HDL / genetics*
  • Male
  • Middle Aged
  • Young Adult

Substances

  • APOL1 protein, human
  • Apolipoprotein L1
  • Apolipoproteins
  • Lipoproteins, HDL