Zusammenfassung
Background Angiotensin II induces vasoconstriction and growth via stimulation of the AT(1) receptor. A genetic variant (+1166A/C) in the 3' untranslated region of this gene had been found to be associated with arterial hypertension, aortic stiffness and coronary artery disease, Objective In order to evaluate further the potential implications of the genetic variability of the AT(1) gene we ...
Zusammenfassung
Background Angiotensin II induces vasoconstriction and growth via stimulation of the AT(1) receptor. A genetic variant (+1166A/C) in the 3' untranslated region of this gene had been found to be associated with arterial hypertension, aortic stiffness and coronary artery disease, Objective In order to evaluate further the potential implications of the genetic variability of the AT(1) gene we explored three newly characterized single nucleotide polymorphisms (SNPs) in its promoter in a Caucasian population-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. For comparison, we genotyped the previously described +1166A/C variant. Results The allele frequencies of the -2228G/A, -1424C/G and -521C/T SNPs were 0.82/0.18, 0.963/0.037 and 0.64/0.36, respectively. Statistical analysis by one-factor ANOVA revealed no significant relationship of any allele, genotype or haplotype with age, sex, body mass index, heart rate, systolic or diastolic blood pressure, hypertension, the intake of antihypertensive medication or left ventricular mass. Likewise, renin, angiotensinogen, angiotensin-converting enzyme, aldosterone or atrial natriuretic peptide levels were not found to be associated with any of these SNPs, Surprisingly, the -2228 A allele was found to be overrepresented in subjects with diabetes mellitus (n = 25, P = 0.006), However, this result could not be confirmed when additional individuals with diabetes mellitus (n = 45) were analysed. A weak linkage disequilibrium was observed between the -2228 A allele and the +1166 C allele (chi(2) 13.1; P = 0.010). Conclusion From the present data it is unlikely that any one of the nine newly characterized SNPs in the promoter region of AT(1) gene is associated with arterial hypertension. J Hypertens 2000, 18:267-272 (C) Lippincott Williams & Wilkins.
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