Hypertensive APOL1 risk allele carriers demonstrate greater blood pressure reduction with angiotensin receptor blockade compared to low risk carriers

English version

Autoři: Patrick N. Cunningham ^aff001; Zhiying Wang ^aff002; Megan L. Grove ^aff002; Rhonda M. Cooper-DeHoff ^aff003; Amber L. Beitelshees ^aff004; Yan Gong ^aff003; John G. Gums ^aff003; Julie A. Johnson ^aff003; Stephen T. Turner ^aff005; Eric Boerwinkle ^aff002; Arlene B. Chapman ^aff001
Působiště autorů: Section of Nephrology, University of Chicago, Chicago, Illinois, United States of America ^aff001; Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, United States of America ^aff002; Department of Pharmacotherapy and Translational Research, College of Pharmacy and Division of Cardiovascular Medicine, College of Medicine, University of Florida, Gainesville, Florida, United States of America ^aff003; Endocrinology, Diabetes, and Nutrition Division, Department of Medicine, University of Maryland, Baltimore, Maryland, United States of America ^aff004; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States of America ^aff005; Baylor College of Medicine, Human Genome Sequencing Center, Houston, Texas, United States of America ^aff006
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0221957

Souhrn

Background

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.

Klíčová slova:

Biology and life sciences – Genetics – Genomics – Genome analysis – Heredity – Genetic mapping – Computational biology – Genetic loci – Anatomy – Medicine and health sciences – Alleles – Genome-wide association studies – Human genetics – Pharmacology – Drugs – Vascular medicine – Renal system – Kidneys – Blood pressure – Hypertension – Antihypertensives – Variant genotypes – Diuretics

Zdroje

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