title: Sex-specific effects of ACE I/D and AGT-M235T on pulse pressure: the HyperGEN Study.
abstract: Evidence shows that an elevated pulse pressure (PP) may lead to an increased risk of cardiovascular morbidity and mortality. There is also evidence that PP is a sexually dimorphic trait, and that genetic factors influence inter-individual variation in PP. The aim of this project was to assess the genotype-by-sex interaction on PP in a sample of mostly hypertensive African American and White participants using candidate genes involved in the renin-angiotensin-aldosterone system. Subjects were participants in the HyperGEN Study, including men (43%) and women (57%) over the age of 55 years (mean age = 65). Candidate gene polymorphisms used were ACE insertion/deletion (1,789 subjects genotyped) and AGT-M235T (1,800 subjects genotyped). We employed linear regression methods to assess the genotype-by-sex interaction. For ACE, genotype-by-sex interaction on PP was detected (P = 0.04): the "D/D" genotype predicted a 2.2 mmHg higher pulse pressure among women, but a 1.2 mmHg lower PP among men, compared to those with an "I" allele, after adjusting for age, weight, height, ethnicity, and antihypertension medication use. A similar interaction was found for systolic blood pressure. The genotype-by-sex interaction was consistent across ethnicity. The interaction was evident among those on antihypertensive medications (P = 0.05), but not among those not taking such medications (P = 0.55). In our analysis of AGT, no evidence of a genotype-by-sex interaction affecting PP, SBP, or DBP was detected. This evidence for a genotype-by-sex interaction helps our understanding of the complex genetic underpinnings of blood pressure phenotypes.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Amy I
authors.initials: AI
authors.lastname: Lynch
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
authors.forename: Michael B
authors.initials: MB
authors.lastname: Miller
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.forename: John H
authors.initials: JH
authors.lastname: Eckfeldt
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hunt
authors.forename: Dabeeru C
authors.initials: DC
authors.lastname: Rao
authors.forename: Luc
authors.initials: L
authors.lastname: Djoussé
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000808:Angiotensinogen / Q000235:genetics*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000235:genetics*; D016021:Epidemiologic Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D054643:INDEL Mutation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D012727:Sex Characteristics
chemical_list: D000959:Antihypertensive Agents; D000808:Angiotensinogen; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A