Essential hypertension and Arg16Gly polymorphism of β2-adrenergic receptor gene


Authors: M. Jáchymová 1;  K. Horký 2;  A. Jindra 1;  J. Peleška 3;  J. Bultas 2;  A. Linhart 2;  Z. Hlubocká 2;  S. Heller 2;  M. Pavlikova 3
Authors‘ workplace: Laboratoř molekulární kardiologie Ústavu klinické biochemie a laboratorní diagnostiky 1. lékařské fakulty UK a VFN, Praha, přednosta prof. MUDr. Tomáš Zima, DrSc. 1;  II. interní klinika kardiologie a angiologie 1. lékařské fakulty UK a VFN, Praha, přednosta prof. MUDr. Michael Aschermann, DrSc., FESC 2;  EuroMISE Centrum, Praha, přednostka prof. RNDr. Jana Zvárová, DrSc. 3
Published in: Vnitř Lék 2005; 51(9): 945-949
Category: Original Contributions

Overview

Study objective:
Sympathetic-adrenal activity plays important role in multifactorial pathogenesis of essential hypertension. Tissue effect of catecholamines is mediated by adrenergic receptors. Vasodilatation action of β2-adrenergic receptors participates in BP regulation. Variations in their structure may lead to the limitation of vasodilatation efficiency and thereby to genesis of hypertension. Consequently polymorphism of β2-adrenergic receptor gene seems to be a promising candidate gene for an analysis of its association with essential hypertension.

Patients’ population and methods:
In this study we investigated the effect of association of Arg16Gly polymorphism of β2-adrenergic receptor gene with the incidence and degree of hypertension. We compared frequency of individual genotypes (GG, AG, AA) and alleles (G and A) in 3 groups of middle-aged individuals: a) a control group with normal BP ≤ 140/90 mm Hg (N, n = 122), b) patients with hypertension well-controlled with antihypertension treatment (KH, n = 156) and c) a group of hypertonic patients resistant to the combination of the three antihypertensives (RH, n = 73). We determined Arg16Gly polymorphism of β2-adrenergic receptor gene by the PCR method on leukocyte DNA with subsequent incubation with restriction enzyme Ncol. We separated resulting fragments by means of electrophoresis on 3% Metaphore agarose gel stained with ethidium bromide. Kruskal-Wallis test (ANOVA), Fisher exact test, χ2 test and linear association test were used for statistical comparison of genotypes and alleles distribution between individual groups.

Results:
We did not find significant differences in representation of number of genotypes and allele frequency between individual monitored groups. However after pooling of KH and RH groups in one group (n = 229 patients) significant difference was found in allele frequency in pooled group of hypertonic patients versus normotonic patients (χ2 = 4.5, p = 0.035). This observation was in accord with the linear association test between the degree of hypertension and allele A incidence (5% significance level) with a shift to lower representation of allele A in higher degrees of hypertension (RH). During the evaluation of mean BP values the tendency to lower values of systolic and also diastolic BP was found, starting from GG genotype, over GA to AA genotype.

Conclusions:
Our recent observations support the hypothesis that genetic variation of β2-adrenergic receptor gene (Arg16Gly polymorphism) can participate in affecting of BP level in combination with other factors and thus it can contribute to a genesis of the essential hypertension.

Key words:
essential hypertension – polymorphism – β2-adrenergic receptor – pathogenetic participation


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Labels
Diabetology Endocrinology Internal medicine
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