Antihypertensive therapy, the alpha-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.
Davis
B R
BR
School of Public Health, University of Texas-Houston, Houston, TX 77030, USA. barry.r.davis@uth.tmc.edu
Arnett
D K
DK
Boerwinkle
E
E
Ford
C E
CE
Leiendecker-Foster
C
C
Miller
M B
MB
Black
H
H
Eckfeldt
J H
JH
D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D002752:Chlorthalidone / Q000627:therapeutic use; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control*; D004311:Double-Blind Method; D017292:Doxazosin / Q000627:therapeutic use; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005998:Glycine; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D015994:Incidence; D053208:Kaplan-Meier Estimate; D017706:Lisinopril / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D013997:Time Factors; D016896:Treatment Outcome; D014364:Tryptophan; D000099291:Adducins
D017311:Amlodipine; D000959:Antihypertensive Agents; D002148:Calmodulin-Binding Proteins; D002752:Chlorthalidone; D017292:Doxazosin; D005998:Glycine; D017706:Lisinopril; D014364:Tryptophan; D000099291:Adducins