title: Association of variants in critical core promoter element of angiotensinogen gene with increased risk of essential hypertension in Japanese.
abstract: We examined the association between variants in the core promoter element 1 (AGCE1) of the human angiotensinogen gene (AGT), which acts as a critical regulator of AGT transcription, and the risk for hypertension. One hundred and eighty patients with documented essential hypertension and a family history of hypertension and 194 control subjects without hypertension were selected and frequency matched by age and sex. Genomic DNA from leukocytes was analyzed for genetic variants (position: -20 to -18) in AGCE1. The haplotype in AGCE1 was significantly associated with increased risk of essential hypertension (P<.05). The frequency of subjects with homozygous C allele at position -18(CC/C-18T) was significantly higher in case patients than in control subjects (P<.005), and the evaluated odds ratio for hypertension was 4.2 (95% confidence interval [CI]: 1.4 to 12.8, CC/C-18T versus CT/C-18T). The homozygous threonine allele at codon 235 (TT/M235T) in exon 2 of AGT was also associated with hypertension (P<.02; odds ratio, TT versus other genotypes, 1.8; 95% CI, 1.1 to 2.7). According to haplotype analysis between AGT polymorphisms, we identified linkage disequilibrium between M235T and A-20C and between M235T and C-18T. We conclude that C-18T polymorphism in AGCE1 is a genetic risk factor for essential hypertension in the Japanese and is more tightly and directly associated with hypertension than TT/M235T.
authors.affiliation: Department of Geriatric Medicine, Osaka University Medical School, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Katsuya
authors.forename: H
authors.initials: H
authors.lastname: Rakugi
authors.forename: S
authors.initials: S
authors.lastname: Takami
authors.forename: Y
authors.initials: Y
authors.lastname: Nakata
authors.forename: T
authors.initials: T
authors.lastname: Miki
authors.forename: J
authors.initials: J
authors.lastname: Higaki
authors.forename: T
authors.initials: T
authors.lastname: Ogihara
mesh_terms: D000368:Aged; D000483:Alleles; D000808:Angiotensinogen / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012016:Reference Values; D012307:Risk Factors
chemical_list: D000808:Angiotensinogen