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

Apolipoprotein L1 Variants and Blood Pressure Traits in African Americans

Girish N Nadkarni  1 , Geneviève Galarneau  1 , Stephen B Ellis  1 , Rajiv Nadukuru  1 , Jinglan Zhang  1 , Stuart A Scott  1 , Claudia Schurmann  1 , Rongling Li  2 , Laura J Rasmussen-Torvik  3 , Abel N Kho  3 , M Geoffrey Hayes  4 , Jennifer A Pacheco  3 , Teri A Manolio  2 , Rex L Chisholm  3 , Dan M Roden  5 , Joshua C Denny  5 , Eimear E Kenny  1 , Erwin P Bottinger  6
Affiliations

Apolipoprotein L1 Variants and Blood Pressure Traits in African Americans

Girish N Nadkarni et al. J Am Coll Cardiol. .

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.

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Figures

FIGURE 1
FIGURE 1. Age at First Diagnosis of Hypertension
Apolipoprotein L1 (APOL1) variant allele homozygotes (orange) were younger at diagnosis of hypertension than APOL1 ancestral allele homozygotes and variant allele heterozygotes (blue). A Cox proportional hazards analysis with age at hypertension diagnosis adjusted for year of birth, sex, and overall mean body mass index was significant in both the discovery cohort and replication meta-analysis.
FIGURE 2
FIGURE 2. Change of Blood Pressure and eGFR
Variations in (A) systolic blood pressure, (B) diastolic blood pressure, and (C) estimated glomerular filtration rate (eGFR) were seen in apolipoprotein L1 (APOL1) ancestral allele homozygotes and APOL1 variant allele heterozygotes versus APOL1 variant allele homozygotes for all cohorts combined between the ages of 20 and 39 years. Line graphs show mean values with 95% confidence intervals. *p < 0.05; **p < 0.01. n.s. = not significant.
CENTRAL ILLUSTRATION
CENTRAL ILLUSTRATION. APOL1 Genotypes and Phenotypic Data From EMRs
Hypertension-related health problems affect African Americans (AAs) to a greater degree than other groups, and apolipoprotein L1 (APOL1) risk variants are associated with kidney disease in hypertensive AAs. Analyzing data from electronic medical records (EMRs) from 3 major health systems in discovery and replication cohorts using recessive and additive models demonstrated that APOL1 risk alleles were associated with higher systolic blood pressure in AAs of 20 to 39 years of age and younger at diagnosis of hypertension.
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