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

The Pharmacogenomics Journal volume 7, pages 112–122 (2007)Cite this article

Abstract

In a double-blind, outcome trial conducted in hypertensive patients randomized to chlorthalidone (C), amlodipine (A), lisinopril (L), or doxazosin (D), the α-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 α-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.

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Authors and Affiliations

  1. School of Public Health, University of Texas-Houston, Houston, TX, USA

    B R Davis, E Boerwinkle & C E Ford

  2. Department of Epidemiology, University of Alabama, Birmingham, AL, USA

    D K Arnett

  3. Fairview-University Medical Center, Minneapolis, MN, USA

    C Leiendecker-Foster & J H Eckfeldt

  4. Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA

    M B Miller

  5. Rush Presbyterian-St Luke's Medical Center, Chicago, IL, USA

    H Black

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  1. B R Davis
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Correspondence to B R Davis.

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Davis, B., Arnett, D., Boerwinkle, E. et al. Antihypertensive therapy, the α-adducin polymorphism, and cardiovascular disease in high-risk hypertensive persons: the Genetics of Hypertension-Associated Treatment Study. Pharmacogenomics J 7, 112–122 (2007). https://doi.org/10.1038/sj.tpj.6500395

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  • DOI: https://doi.org/10.1038/sj.tpj.6500395

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