Hypertensive APOL1 risk allele carriers demonstrate greater blood pressure reduction with angiotensin receptor blockade compared to low risk carriers
PublisherPublic Library of Science
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AbstractBackground: Hypertension (HTN) disproportionately affects African Americans (AAs), who respond better to thiazide diuretics than other antihypertensives. Variants of the APOL1 gene found in AAs are associated with a higher rate of kidney disease and play a complex role in cardiovascular disease. Methods: AA subjects from four HTN trials (n = 961) (GERA1, GERA2, PEAR1, and PEAR2) were evaluated for blood pressure (BP) response based on APOL1 genotype after 4–9 weeks of monotherapy with thiazides, beta blockers, or candesartan. APOL1 G1 and G2 variants were determined by direct sequencing or imputation. Results: Baseline systolic BP (SBP) and diastolic BP (DBP) levels did not differ based on APOL1 genotype. Subjects with 1–2 APOL1 risk alleles had a greater SBP response to candesartan (-12.2 +/- 1.2 vs -7.5 +/- 1.8 mmHg, p = 0.03; GERA2), and a greater decline in albuminuria with candesartan (-8.3 +/- 3.1 vs +3.7 +/- 4.3 mg/day, p = 0.02). APOL1 genotype did not associate with BP response to thiazides or beta blockers. GWAS was performed to determine associations with BP response to candesartan depending on APOL1 genotype. While no SNPs reached genome wide significance, SNP rs10113352, intronic in CSMD1, predicted greater office SBP response to candesartan (p = 3.7 x 10−7) in those with 1–2 risk alleles, while SNP rs286856, intronic in DPP6, predicted greater office SBP response (p = 3.2 x 10−7) in those with 0 risk alleles. Conclusions: Hypertensive AAs without overt kidney disease who carry 1 or more APOL1 risk variants have a greater BP and albuminuria reduction in response to candesartan therapy. BP response to thiazides or beta blockers did not differ by APOL1 genotype. Future studies confirming this initial finding in an independent cohort are required. Copyright 2019 Cunningham et al.
SponsorsPEAR1 and PEAR2 was supported by a grant from the National Institutes of Health (https://www.nih.gov/), grant U01 GM074492, funded as part of the Pharmacogenetics Research Network (JAJ). P
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85072280673&doi=10.1371%2fjournal.pone.0221957&partnerID=40&md5=971e84dac877c269d7fedc823db36cba; http://hdl.handle.net/10713/11025
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