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Mol Genet Genomic Med. 2019 Aug 13:e788. doi: 10.1002/mgg3.788. [Epub ahead of print]

Genome-wide meta-analysis of SNP and antihypertensive medication interactions on left ventricular traits in African Americans.

Author information

1
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
2
Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, USA.
3
Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
4
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.
5
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
6
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
7
Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
8
School of Biomedical Informatics, University of Texas Health Sciences Center at Houston, Houston, Texas, USA.
9
Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Seattle, Washington, USA.
10
Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, Washington, USA.
11
Kaiser Permanente Washington Health Research Institute, Seattle, Washington, USA.
12
Cardiovascular Health Research Unit, Division of Cardiology, Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington, USA.
13
Department of Preventive Medicine Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
14
Department of Medicine, University of Colorado Denver, Aurora, Colorado, USA.
15
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA.
16
Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
17
Departments of Medicine and Preventive Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
18
College of Public Health, University of Kentucky, Lexington, Kentucky, USA.

Abstract

BACKGROUND:

Left ventricular (LV) hypertrophy affects up to 43% of African Americans (AAs). Antihypertensive treatment reduces LV mass (LVM). However, interindividual variation in LV traits in response to antihypertensive treatments exists. We hypothesized that genetic variants may modify the association of antihypertensive treatment class with LV traits measured by echocardiography.

METHODS:

We evaluated the main effects of the three most common antihypertensive treatments for AAs as well as the single nucleotide polymorphism (SNP)-by-drug interaction on LVM and relative wall thickness (RWT) in 2,068 participants across five community-based cohorts. Treatments included thiazide diuretics (TDs), angiotensin converting enzyme inhibitors (ACE-Is), and dihydropyridine calcium channel blockers (dCCBs) and were compared in a pairwise manner. We performed fixed effects inverse variance weighted meta-analyses of main effects of drugs and 2.5 million SNP-by-drug interaction estimates.

RESULTS:

We observed that dCCBs versus TDs were associated with higher LVM after adjusting for covariates (p = 0.001). We report three SNPs at a single locus on chromosome 20 that modified the association between RWT and treatment when comparing dCCBs to ACE-Is with consistent effects across cohorts (smallest p = 4.7 × 10-8 , minor allele frequency range 0.09-0.12). This locus has been linked to LV hypertrophy in a previous study. A marginally significant locus in BICD1 (rs326641) was validated in an external population.

CONCLUSIONS:

Our study identified one locus having genome-wide significant SNP-by-drug interaction effect on RWT among dCCB users in comparison to ACE-I users. Upon additional validation in future studies, our findings can enhance the precision of medical approaches in hypertension treatment.

KEYWORDS:

GWAS; antihypertensive treatment; left ventricular trait; pharmacogenetics

PMID:
31407531
DOI:
10.1002/mgg3.788
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