title: Sex-specific effects of AGT-6 and ACE I/D on pulse pressure after 6 months on antihypertensive treatment: the GenHAT study.
abstract: Research suggests pulse pressure (PP) is a predictor of cardiovascular disease, and genes likely influence PP levels. Additionally, gender may be an effect modifier between PP and cardiovascular disease. This study addresses whether two renin-angiotensin-aldosterone system (RAAS) variants are associated with PP in a sex-specific manner (genotype-by-sex interaction). Subjects comprised 35,048 GenHAT study participants over 55 years old, approximately half were women and half non-Hispanic white. Blood pressure measurements were obtained 6 months after randomization to one of four antihypertensive medications. The polymorphisms considered were AGT-6 and ACE-I/D. We employed linear regression to assess the interaction. AGT-6 showed a significant (p < 0.001) genotype-by-sex interaction. Men with the 'G/G' genotype had a higher PP (0.6 mm HG) than men carrying an 'A' allele, while 'G/G' women had a lower PP (0.7 mm Hg) than women carrying an 'A' allele. Three of the four treatment groups (chlorthalidone, amlodipine and lisinopril) suggested a consistent interaction in sub-group analyses (only amlodipine was statistically significant, p < 0.001), whereas doxazosin did not. The interaction was evident among non-Hispanic participants but not among Hispanic participants. For ACE-I/D no evidence for a genotype-by-sex interaction was detected. This finding of genotype-by-sex interaction on PP helps our understanding of the complexity of genetic effects on blood pressure.
authors.affiliation: University of Minnesota, Department of Laboratory Medicine and Pathology, Minneapolis, Minnesota, USA.
authors.forename: A I
authors.initials: AI
authors.lastname: Lynch
authors.forename: D K
authors.initials: DK
authors.lastname: Arnett
authors.forename: B R
authors.initials: BR
authors.lastname: Davis
authors.forename: E
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: C E
authors.initials: CE
authors.lastname: Ford
authors.forename: J H
authors.initials: JH
authors.lastname: Eckfeldt
authors.forename: C
authors.initials: C
authors.lastname: Leiendecker-Foster
mesh_terms: D000368:Aged; D000808:Angiotensinogen / Q000235:genetics*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D017384:Sequence Deletion; D012727:Sex Characteristics
chemical_list: D000959:Antihypertensive Agents; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A