Document Detail


Population-based sample reveals gene-gender interactions in blood pressure in White Americans.
MedLine Citation:
PMID:  17159089     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The influence of genetic contributors, such as common single nucleotide polymorphisms, on blood pressure and essential hypertension may vary with the gender. We used the power of a large, community-based sample to probe whether gender interacts with genes in contributing to extremes of blood pressure in 611 male and 656 female age-matched white Americans within the top and bottom 5th percentiles of blood pressure among >53 000 people in a health maintenance program. This approach has >90% statistical power to detect genes contributing as little as 3% to trait (blood pressure) variation. We scored approximately 60 000 genotypes in the subjects: 48 single nucleotide polymorphisms at 33 autosomal and 2 X-linked genes in adrenergic and renal pathways that regulate blood pressure. Six individual variants significantly affected blood pressure and demonstrated gene-by-gender interaction, yielding different effects of the single nucleotide polymorphism on blood pressure in males and females. In females, polymorphisms at beta(1)-adrenergic receptor and alpha(2A)-adrenergic receptor contributed to blood pressure, whereas in men, polymorphisms at beta(2)-adrenergic receptor and angiotensinogen were associated. An alpha(2A)-adrenergic receptor haplotype influenced blood pressure in women, whereas 2 angiotensinogen haplotypes were associated in men. We also detected gene-by-gene, gender-specific interactions (epistasis) in pathophysiological pathways. This study reveals gender-specific effects of single nucleotide polymorphisms, haplotypes, and gene-by-gene interactions that determine blood pressure in white Americans. Such genetic variants may define genetically and etiologically distinct subgroups of men and women with essential hypertension and may have implications for rational treatment selection.
Authors:
Brinda K Rana; Paul A Insel; Samuel H Payne; Kenneth Abel; Ernest Beutler; Michael G Ziegler; Nicholas J Schork; Daniel T O'Connor
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-12-11
Journal Detail:
Title:  Hypertension     Volume:  49     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2006-12-22     Completed Date:  2007-01-16     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  96-106     Citation Subset:  IM    
Affiliation:
Department of Psychiatry, University of California at San Diego, La Jolla, CA 92093, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Alleles
Angiotensinogen / genetics
Antihypertensive Agents / therapeutic use
Blood Pressure / genetics*
Diastole
Epistasis, Genetic*
European Continental Ancestry Group / genetics*
Female
Genes, X-Linked
Genotype
Haplotypes
Humans
Hypertension / drug therapy,  genetics,  physiopathology*
Male
Middle Aged
Polymorphism, Single Nucleotide*
Receptors, Adrenergic / genetics
Sex Factors*
United States
Grant Support
ID/Acronym/Agency:
HL58120/HL/NHLBI NIH HHS; HL69758/HL/NHLBI NIH HHS; RR00827/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Receptors, Adrenergic; 11002-13-4/Angiotensinogen

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


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