title: Association of angiotensin II type 2 receptor gene variant with hypertension.
abstract: The renin-angiotensin system plays an important role in blood pressure regulation by influencing salt-water homeostasis and vascular tone. Angiotensin II, the major biologically active component of this system, exerts its effect via two pharmacologically distinct subtypes of angiotensin II receptors, the angiotensin II type 1 receptor (AT1-R) and the angiotensin II type 2 receptor (AT2-R). Thus, the AT2-R gene may be involved in hypertension. Accordingly, our objective was to examine whether polymorphisms of the AT2-R gene are involved in hypertension. The entire AT2-R gene including the promoter region was screened to find polymorphisms. As a result, two novel single nucleotide polymorphisms (SNPs), A1818T in intron 2 and G4303A in exon 3, as well as two known SNPs, A1675G in intron 1 and C4599A in exon 3, were identified. These four SNPs had similar allele frequencies, and the A1675G and C4599A polymorphisms were in almost complete linkage disequilibrium. Because the AT2-R gene is located on the X chromosome, we analyzed the possible association between the C4599A polymorphism and hypertension in men and in women separately in two large Japanese populations. This analysis showed that the C4599A polymorphism was associated with hypertension in women (p=0.0058), but not in men. Moreover, this female-specific association was pronounced in premenopausal women. The female-specific association may be helpful in conducting further molecular and biological studies on the relationship among sex, the renin-angiotensin system, and hypertension.
authors.affiliation: Department of Geriatric Medicine, School of Medicine, Ehime University, Onsen-gun, Ehime, Japan.
authors.forename: Jing-Ji
authors.initials: JJ
authors.lastname: Jin
authors.forename: Jun
authors.initials: J
authors.lastname: Nakura
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wu
authors.forename: Miyuki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Michiko
authors.initials: M
authors.lastname: Abe
authors.forename: Yusen
authors.initials: Y
authors.lastname: Chen
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tabara
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Michiya
authors.initials: M
authors.lastname: Igase
authors.forename: Xiao
authors.initials: X
authors.lastname: Bo
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Kohara
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
mesh_terms: D000225:Adenine; D000328:Adult; D044466:Asian People / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics; D003596:Cytosine; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics
chemical_list: D044139:Receptor, Angiotensin, Type 2; D003596:Cytosine; D000225:Adenine