P484Is the hypertrophy of left ventricle in aortic stenosis modified by the polymorphism of the gen of the receptor type 2 for bradykinin?

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It has been shown during the past few years by experiments onanimals that bradykinin (BK) is an inhibitor of growth of cardiomyocytes. Ahypothesis is even postulated, that anti-mitogenic effect of ACE inhibitiorsactivity is connected with the increase of concentration of locally producedBK. From among numerous polymorphisms of the gen of the receptor type 2 (pBK2R)polymorphism + 9/-9 of exon 1 is connected with the expression of receptorprotein. For people with an allele -9 (D - deletion 9bp)the synthesis mRNA for BK2R is bigger than for carriers of the allele + 9 (allel I).

The aim of the study was to estimate the frequencies of thegenetic BK2R polymorphism + 9/-9 in patients with aortic stenosis (AS) andthe influence of this polymorphism on the degree of the hypertrophy of left ventricle(LVH) and the range of its regression after an aortic valve replacement (AVR).


475 pts (43% of whom were women) with an average age of 65 ( + /-plus10) yrs qualified for AVR due to significant, isolated AS thepBK2R influence on the degree of LVH before and after AVR has been estimated.All pts had an echo examination in which: the aortic gradient (MGA), the left ventricle massindex (LVMI), PSI (the sum of thickness of the posterior wall and interventricularseptum index) have been assessed.

The results

It has been shown that in the group of patients with AS the estimated frequency of the allele + 9/-9 (I/D) pBK2R wascompatible with the Hardy-Weinberg rule and amounted to 28% II, 53% DI and 19%DD (it was similiar for both men and women). A relation between the size of LVMI and pBK2R (p=0.049) was shown.The degree of LVH was also influenced by the degree of AS (p=0.0001), arterialhypertension (p=0.044) and the sex (p=0.0001). In the mutli-factor analysisonly sex (p=0.0001) and the degree of AS (p=0.0001) appeared to be significantparameters. The PSI was significantly influenced by: pBK2R (p=0.009), sex (p=0.0001),age (p=0.03) and the degree of AS (p=0.0001). In the multi-factor analysis thefollowing parameters appeared to be significant: the degree of AS (p=0.0001),sex (p=0.0001) and pBK2R (p=0.014).The analysis of the relation between the reduction of LVH with pBK2Rshowed a significant correlation both for reduction of LVMI (p=0.02) andfor reduction of PSI (p=0.001). The dependence has been confirmed in the multi-factoranalysis.


Genetical polymorphism of the receptor type 2 for bradykinin is anidependant factor that modulates the size of the hypertrophy of left venctriclein patients with aortic stenosis.

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