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 .