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Title: Influence of polymorphisms of paraoxonase and ATP2A2 genes on presence of ventricular arrythmias in coronary artery disease

Abstract:

This doctoral dissertation presents the examination of the association between polymorphisms of paroxonase ( PON1) gene and ATP-dependent Calcium pump of the endoplasmic reticulum SERCA2a (ATP2A2) gene promotor areas. Paroxonase ( PON1) is an essential component of HDL fraction of serum lipoproteids providing antioxidant activity and therefore preventing production of free radicles and oxidative modification of lipoproteids ( including LDL fraction). That is one of the essential mechanisms that curb coronary atherosclerosis. The main role of SERCA2a transporter is to restore the low calcium level during cardiomyocyte relaxation immediately so as to make the next cardiac-muscle contraction hemodynamically effective. Based on studies, a hypothesis has been formulated indicating that polymorphisms in these genes may be correlated with incidence of ventricular arrhytmias in the course of advanced coronary heart disease ( CHD) ( peri-infarction period and postinfarct phase). An increase in intracellular calcium level has a positive inotropic action and the relationship between PON-1 gene polymorphism and progression of atherosclerosis has been proved and shown to be a risk factor of CHD. The study included 60 patients with CHD who were divided into 2 separate groups according to presence or lack of ventricular arrhytmias. A number of investigations has been conducted to examine all patients to examine them for CHD: resting electrocardiography, treadmill exercise electrocardigraphy, echocardiogram and invasive examination of coronary arteries – coronarography. A number of the laboratory tests of blood plasm that have conducted to assess risk factors of CHD: glucose level, glucose tolerance test if necessary, lipid profile, electrolytes levels. Additionally BMI has been measured na arterial blood pressure taken. A specimen of full vein blood has been taken to isolate DNA out of leucocytes with the view to investigating polymorphisms. The isolated genetic material has ben amplified using PCR method and then treated with restriction enzymes and the fragments obtained were separated by electrophoresis (RFLP method). Using the above procedure the incidence of particular alleles of examined polymorphisms of promotor regions, 108T/C in PON1gene and -491C/G of ATP2A2 in gene, has been investigated. Next statistical analyses were conducted to compare the incidence of particular genotypes in both groups and to assess the relationship between risk factors and alleles and incidence of ventricular arrhytmias. No statistically significant differences between the two examined groups were revealed in terms of incidence of particular alleles in the examined polmorphisms of PON1 and ATP2A2 genes and in terms of genotype distribution. The evidence from the study did not show any difference between the two groups, with and without comorbid ventricular arrhytmias, in relation to the examined polymorphisms of both genes. However within the group of patients with ventricular arrhytmias it has been revealed that the presence of allel G of polymorphism of ATP2A2 gene is strongly correlated with elevated systolic blood pressure and enhanced left ventricle ejection fraction. No direct relationship between any of polymorphisms of the examined genes and the incidence of ventricular arrhytmias in the course of CHD has been proved, but as the hypothesis of ventricular arrhytmias being a special manifestation of CHD reflecting the severity of atherosclerosis is commonly recognized it is advisable to conduct a similar analysis within a larger group of patients and taking other polymorphisms changing the function of SERCA2A proteins ( e.g., phospholamban), not examined in this study, into account as well. The another reason justifying the need for further investigation is the fact that within the whole group of patients examined the genotype increasing the propensity for the development of atherosclerosis was predominant.

Level of degree:

2 - studia doktoranckie

Degree discipline:

choroby układu krążenia ; genetyka

Degree grantor:

Wydział Lekarski

Promoter:

Aldona Dembińska-Kieć

Date issued:

2008

Format:

application/pdf

Identifier:

oai:dl.cm-uj.krakow.pl:852

Call number:

ZB-108812

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Access rights:

tylko w bibliotece

Location of original object:

Biblioteka Medyczna Uniwersytetu Jagiellońskiego - Collegium Medicum

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Last modified:

Nov 18, 2019

In our library since:

Nov 21, 2012

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All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/852

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ZB-108812 Nov 18, 2019
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