Evaluation of three polymorphisms in the promoter region of the angiotensin II type I receptor gene

Background Angiotensin II induces vasoconstriction and growth via stimulati on of the AT(1) receptor. A genetic variant (+1166A/C) in the 3' untranslat ed region of this gene had been found to be associated with arterial hypert ension, aortic stiffness and coronary artery disease, Objective In order to evaluate further the potential implications of the ge netic variability of the AT(1) gene we explored three newly characterized s ingle nucleotide polymorphisms (SNPs) in its promoter in a Caucasian popula tion-based sample (n = 623). One of these (-2228G/A) is in complete linkage disequilibrium with six additional SNPs in the region such that indirectly , potential functional implications of these sites were assessed as well. F or comparison, we genotyped the previously described +1166A/C variant. Results The allele frequencies of the -2228G/A, -1424C/G and -521C/T SNPs w ere 0.82/0.18, 0.963/0.037 and 0.64/0.36, respectively. Statistical analysi s by one-factor ANOVA revealed no significant relationship of any allele, g enotype or haplotype with age, sex, body mass index, heart rate, systolic o r diastolic blood pressure, hypertension, the intake of antihypertensive me dication or left ventricular mass. Likewise, renin, angiotensinogen, angiot ensin-converting enzyme, aldosterone or atrial natriuretic peptide levels w ere not found to be associated with any of these SNPs, Surprisingly, the -2 228 A allele was found to be overrepresented in subjects with diabetes mell itus (n = 25, P = 0.006), However, this result could not be confirmed when additional individuals with diabetes mellitus (n = 45) were analysed. A wea k linkage disequilibrium was observed between the -2228 A allele and the +1 166 C allele (chi(2) 13.1; P = 0.010). Conclusion From the present data it is unlikely that any one of the nine ne wly characterized SNPs in the promoter region of AT(1) gene is associated w ith arterial hypertension. J Hypertens 2000, 18:267-272 (C) Lippincott Will iams & Wilkins.