Hypertensive APOL1 risk allele carriers demonstrate greater blood pressure reduction with angiotensin receptor blockade compared to low risk carriers
| العنوان: | Hypertensive APOL1 risk allele carriers demonstrate greater blood pressure reduction with angiotensin receptor blockade compared to low risk carriers |
|---|---|
| المؤلفون: | John G. Gums, Yan Gong, Eric Boerwinkle, Patrick N. Cunningham, Megan L. Grove, Zhiying Wang, Julie A. Johnson, Amber L. Beitelshees, Rhonda M. Cooper-DeHoff, Arlene B. Chapman, Stephen T. Turner |
| المصدر: | PLoS ONE, Vol 14, Iss 9, p e0221957 (2019) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, Angiotensin receptor, Heredity, Pharmacogenomic Variants, 030232 urology & nephrology, Tetrazoles, Blood Pressure, 030204 cardiovascular system & hematology, Vascular Medicine, Genome-wide association studies, 0302 clinical medicine, Genotype, Medicine and Health Sciences, Diuretics, Multidisciplinary, Drugs, Genomics, Middle Aged, Apolipoprotein L1, 3. Good health, Genetic Mapping, Treatment Outcome, Hypertension, Blood pressure, Medicine, Female, Anatomy, medicine.symptom, Research Article, medicine.drug, Adult, medicine.medical_specialty, Science, Variant Genotypes, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, 03 medical and health sciences, Internal medicine, Genome-Wide Association Studies, Genetics, medicine, Humans, Variant genotypes, Alleles, Thiazide, Pharmacology, business.industry, Biphenyl Compounds, Biology and Life Sciences, Computational Biology, Human Genetics, Kidneys, Sequence Analysis, DNA, Renal System, Genome Analysis, medicine.disease, Black or African American, Candesartan, Endocrinology, Genetic Loci, Albuminuria, Benzimidazoles, business, Angiotensin II Type 1 Receptor Blockers, Genome-Wide Association Study, Antihypertensives, Kidney disease |
| الوصف: | © 2019 Cunningham et al. 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. PEAR1 and PEAR2 was supported by a grant from the National Institutes of Health (https://www.nih.govTest/), grant U01 GM074492, funded as part of the Pharmacogenetics Research Network (JAJ). PEAR1 was also supported by the following grants from the NIH National Center for Research Resources: grant M01 RR00082 and UL1 RR029890 to the University of Florida, grants UL1 RR025008 and M01 RR00039 (ABC) to Emory University, and UL1 RR024150 to Mayo Clinic. PEAR2 was also supported by the National Center for Advancing Translational Sciences under the award number UL1 TR000064 (University of Florida); UL1 TR000454 (Emory University) and UL1 TR000135 (Mayo Clinic), and the Mayo Foundation. GERA was supported by NIH grants HL74735, HL53330 (STT), and the Mayo Foundation (https://www.mayo.edu/researchTest). |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8d1cbc13b3a177e6e0870bcf2b70303fTest https://doi.org/10.1371/journal.pone.0221957Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8d1cbc13b3a177e6e0870bcf2b70303f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
|---|