[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].
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.


RESULTS
A sample of Czech population (398 individuals), 192 normotensives (age of 45.87 +/- 3.0, BMI = 25.44 +/- 3.31 kg x m2) a 206 hypertensives (age of 48.71 +/- 8.42, BMI = 27.18 +/- 4.16 kg x 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. Chi2 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.
Ustav patologické fyziologie LF MU, Brno. avasku@med.muni.cz
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Vasků
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Soucek
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Znojil
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Kuhrová
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Tschöplová
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Vácha
D000328:Adult; D000808:Angiotensinogen / Q000235:genetics*; D019332:Endothelin-1 / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic
D019332:Endothelin-1; D000808:Angiotensinogen