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Population-based sample reveals gene-gender interactions in blood pressure in White Americans.
- Source :
-
Hypertension (Dallas, Tex. : 1979) [Hypertension] 2007 Jan; Vol. 49 (1), pp. 96-106. Date of Electronic Publication: 2006 Dec 11. - Publication Year :
- 2007
-
Abstract
- 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.
- Subjects :
- Adult
Aged
Alleles
Angiotensinogen genetics
Antihypertensive Agents therapeutic use
Diastole
Female
Genes, X-Linked
Genotype
Haplotypes
Humans
Hypertension drug therapy
Hypertension genetics
Male
Middle Aged
Receptors, Adrenergic genetics
United States
Blood Pressure genetics
Epistasis, Genetic
Hypertension physiopathology
Polymorphism, Single Nucleotide
Sex Factors
White People genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4563
- Volume :
- 49
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Hypertension (Dallas, Tex. : 1979)
- Publication Type :
- Academic Journal
- Accession number :
- 17159089
- Full Text :
- https://doi.org/10.1161/01.HYP.0000252029.35106.67