TY - JOUR
T1 - Antihypertensive therapy, the α-adducin polymorphism, and cardiovascular disease in high-risk hypertensive persons
T2 - The genetics of hypertension-associated treatment study
AU - Davis, B. R.
AU - Arnett, D. K.
AU - Boerwinkle, E.
AU - Ford, C. E.
AU - Leiendecker-Foster, C.
AU - Miller, M. B.
AU - Black, H.
AU - Eckfeldt, J. H.
PY - 2007/4
Y1 - 2007/4
N2 - 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 = 36913). 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.
AB - 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 = 36913). 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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U2 - 10.1038/sj.tpj.6500395
DO - 10.1038/sj.tpj.6500395
M3 - Article
C2 - 16702981
AN - SCOPUS:34147126026
SN - 1470-269X
VL - 7
SP - 112
EP - 122
JO - Pharmacogenomics Journal
JF - Pharmacogenomics Journal
IS - 2
ER -
