1. ¹School of Public Health, University of Texas-Houston, Houston, TX, USA
2. ²Department of Epidemiology, University of Alabama, Birmingham, AL, USA
3. ³Fairview-University Medical Center, Minneapolis, MN, USA
4. ⁴Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA
5. ⁵Rush Presbyterian-St Luke's Medical Center, Chicago, IL, USA

Correspondence: Dr BR Davis, School of Public Health, University of Texas-Houston, 1200 Herman Pressler, Houston, TX 77030, USA. Tel: +1 713 500 9515; Fax: +1 713 500 9530. E-mail: barry.r.davis@uth.tmc.edu

Received 17 November 2005; Revised 16 February 2006; Accepted 17 February 2006; Published online 16 May 2006.

Abstract

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