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Antihypertensive therapy, the alpha-adducin polymorphism, and cardiovascular disease in high-risk hypertensive persons: the Genetics of Hypertension-Associated Treatment Study.

Author(s): Davis BR, Arnett DK, Boerwinkle E, Ford CE, Leiendecker-Foster C, Miller MB, Black H, Eckfeldt JH

Affiliation(s): School of Public Health, University of Texas-Houston, Houston, TX 77030, USA. barry.r.davis@uth.tmc.edu

Publication date & source: 2007-04, Pharmacogenomics J., 7(2):112-22. Epub 2006 May 16.

In a double-blind, outcome trial conducted in hypertensive patients randomized to chlorthalidone (C), amlodipine (A), lisinopril (L), or doxazosin (D), the alpha-adducin Gly460Trp polymorphism was typed (n=36 913). Mean follow-up was 4.9 years. Relative risks (RRs) of chlorthalidone versus other treatments were compared between genotypes (Gly/Gly+Gly/Trp versus Trp/Trp). Primary outcome was coronary heart disease (CHD). Coronary heart disease incidence did not differ among treatments or genotypes nor was there any interaction between treatment and genotype (P=0.660). Subgroup analyses indicated that Trp allele carriers had greater CHD risk with C versus A+L in women (RR=1.31) but not men (RR=0.91) with no RR gender differences for non-carriers (gender-gene-treatment interaction, P=0.002). The alpha-adducin gene is not an important modifier of antihypertensive treatment on cardiovascular risk, but women Trp allele carriers may have increased CHD risk if treated with C versus A or L. This must be confirmed to have implications for hypertension treatment.

Page last updated: 2007-06-01

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