Interaction of Mutations M235T of the Gene for Angiotensinogen and Taq I
8,000 in the Gene for Endothelin-1 at the Onset of Essential Hypertension
Vašků A.,
Ústav patologické fyziologie LF MU, Brno 1 1. interní klinika LF MU, FN u sv. Anny, Brno 2 Výzkumný ústav zdraví dítěte, Brno |
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Abstract:
Background. Identification of mutations contributing to the pathogenesis of essential hypertension performs to
understand deeper consequences of developing pathophysiological changes, to value individual risk of hypertension
in the preclinical stages and, regarding the observed genotype, to choose optimum therapy. The aim of the study was
to prove the existence of difference in double genotype occurrence of polymorphic candidate genes between
normotensive and hypertensive subjects.
Methods and Results. A sample of Czech population (398 individuals), 192 normotensives (age of 45.87±3.0,
BMI=25.44±3.31 kg.m
-2
) a 206 hypertensives (age of 48.71±8.42, BMI=27.18±4.16 kg.m
-2
) was genotyped at
angiotensinogen (AGT, M235T polymorphism, exon 2) and endothelin-1 (EDN-1, Taq I 8000 polymorphism, intron
4) genes by PCR methods. Experimental schedule was case-control. c
2
and Fisher-exact test were used for statistical
analyses. M-allele of angiotensinogen gene was associated with essential hypertension (p=0.0111). Allele (-) alone
at endothelin-1 gene was associated with essential hypertension with marginal significance (p=0.0622). A significant
loss of heterozygotes MT (M235 AGT) at homozygote (--) at endothelin-1 gene (p=0.0025) as well as a significant
increase of allele (-) of endothelin-1 gene at homozygote MM at angiotensinogen gene (p=0.0034) were found.
Conclusions. Interaction of two polymorphic genetic variants of angiotensinogen and endothelin-1 genes was
found. From the pathophysiological point of view, the fact may be explained as a stream to compensate the influence
of variability of other genes more causatively conditioning essential hypertension.
Key words:
24-h blood pressure monitoring, gene polymorphism, angiotensinogen (AGT), endothelin-1 (EDN-1),
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