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Member Research and Reports

Member Research and Reports

UAB Investigators and Team Analyze Drug-Gene Interactions of Antihypertensive Medications

More than 65 million people in the United States have high blood pressure — a known risk factor for such cardiovascular diseases (CVDs) as myocardial infarction and stroke—and many are being treated with hypertensive medications to lessen the chances of future health complications. Dr. Donna K. Arnett, professor and chair in the department of epidemiology at the University of Alabama at Birmingham, and Dr. Joshua C. Bis, research scientist at the University of Washington — leading an international team that included Dr. Ryan Irvin, assistant professor in UAB’s department of epidemiology — recently conducted a genome-wide association study of 21,267 pharmaceutically treated individuals (with such classes of drugs as angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics) to test the hypothesis that genetic variants might affect or alter the efficacy of conventional antihypertensive treatments on major cardiovascular outcomes.

Donna Arnett en las instalaciones del CNIC de Madrid el 13 de mayo de 2013
[Photo: Dr. Donna K. Arnett]

The researchers wrote, “In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases).”

They concluded that “[a]lthough drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (Pinteraction > 5.0×10-8). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genome-wide association studies (Pinteraction ≥ 0.01).” These study results indicate no significant pharmacogenetic influences of common SNPs on blood pressure medications and their link to the risk of CVD.

“Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease: A Pharmacogenomics Study from the CHARGE Consortium” was published in October in PLOS One.

Journal article: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0140496