Document Detail


Sex-specific effects of ACE I/D and AGT-M235T on pulse pressure: the HyperGEN Study.
MedLine Citation:
PMID:  17492314     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Amy I Lynch; Donna K Arnett; James S Pankow; Michael B Miller; Kari E North; John H Eckfeldt; Steven C Hunt; Dabeeru C Rao; Luc Djoussé
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-05-10
Journal Detail:
Title:  Human genetics     Volume:  122     ISSN:  1432-1203     ISO Abbreviation:  Hum. Genet.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-07-04     Completed Date:  2008-04-30     Revised Date:  2008-06-27    
Medline Journal Info:
Nlm Unique ID:  7613873     Medline TA:  Hum Genet     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  33-40     Citation Subset:  IM    
Affiliation:
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Angiotensinogen / genetics*
Antihypertensive Agents / therapeutic use
Blood Pressure / genetics*
Epidemiologic Studies
Female
Gene Frequency
Genotype
Humans
Hypertension / drug therapy,  epidemiology,  ethnology,  genetics
INDEL Mutation* / physiology
Male
Middle Aged
Peptidyl-Dipeptidase A / genetics*
Polymorphism, Single Nucleotide* / physiology
Sex Characteristics*
Grant Support
ID/Acronym/Agency:
HL 54472/HL/NHLBI NIH HHS; HL007972/HL/NHLBI NIH HHS; HL54471/HL/NHLBI NIH HHS; HL54473/HL/NHLBI NIH HHS; HL54495/HL/NHLBI NIH HHS; HL54496/HL/NHLBI NIH HHS; HL54497/HL/NHLBI NIH HHS; HL54509/HL/NHLBI NIH HHS; HL54515/HL/NHLBI NIH HHS; HL55673/HL/NHLBI NIH HHS; M10RR0047-34/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 11002-13-4/Angiotensinogen; EC 3.4.15.1/ACE protein, human; EC 3.4.15.1/Peptidyl-Dipeptidase A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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