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

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.