Quantifizierung von Polymorphismen im Tumor-Nekrose-Alpha Gen und im Interleukin-10 Gen bei Patienten mit dilatativer Kardiomyopathie
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Philipps-Universität Marburg
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Abstract
Many cytokines are involved in the pathogenesis of DCM. In this context especially the pro-inflammatory cytokine TNF-α and the anti-inflammatory cytokine IL-10 play an important role. So a correlation between DCM and the -308 G/A-SNP of the TNF-α gene as well as the -1082 G/A-SNP of the IL-10 gene was shown in some previous studies.
Using polymerase chain-reaction and restriction fragment length polymorphism analysis the frequency of the above mentioned SNPs was examined in a group consisting of 421 patients suffering from DCM and compared with a group of 374 healthy people. In ad-dition an analysis of an association of DCM and the with biometric data and clinical parameters (EF, SF, EDP, HF, LVEDD, EDVI) as well as with fDCM or the presence of Parvovirus B19) with the -308 G/A- SNP and -1082 G/A-SNP was also performed. .
The frequency of the TNFA2 allel was significantly higher in the patients than in the healthy control group (27.94% vs 22.06%, p=0.008). A TNFA2 allel leads to a 1.37-fold higher risk of developing DCM (OR=1.37, 95%-KI=1.089/1.724). Furthermore there exists a significant association of the A/G-genotype with DCM when compared to the G/G-genotype (p=0,001). There is no association of the A/A-genotype with DCM. The -308 G/A-SNP was neither associated with the above mentioned clinical characteristics nor with Parvovirus B19 or fDCM.
Neither IL-10*1A (p=0,81) nor the -1082 A/G- or A/A-genotype (p=0,253) were asso-ciated with the development of a DCM. In contrast, a significant association of the -1082 G/A-SNP with EDP and LVEDD measured in follow-up was found. No associa-tion was found concerning other clinical characteristics.
The results of this study imply that the TNFA2 and the -308 A/G-genotyp in the TNF-α gene are linked to the pathogenesis of DCM in patients living in Germany. There is no association of the -1082 G/A-SNP with the pathogenesis of DCM. As there was shown to be an association of the above mentioned SNP with the EDP and LVEDD in the fol-low-up, there may be an association of the -1082 G/A-SNP with DCM, which was not detected in this study. This should be analyzed in a subsequent study with an even greater number of DCM patients. Due to the fact, that TNFA2 is linked to a higher se-cretion of the pro-inflammatory cytokine TNF-α and IL-10*1A is associated with a lower production of the anti-inflammatory cytokine IL-10, which triggers an inflamma-tion as well as the pathogenesis of DCM, it would be interesting to measure the plasma levels of these cytokines also in subsequent investigations.
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Dates
Created: 2013Issued: 2013-06-12Updated: 2013-06-12
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
dilatative Kardiomyopathiecongestive heart failurePolymorphismenInterleukin 10Tumor necrosis factor alphapolymorphismsdilated cardiomyopathy
DFG-subjects
Interleukin 10Kongestive HerzmuskelkrankheitTumor-Nekrose-Faktor
DDC-Numbers
610
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Pietz, Daniela: Quantifizierung von Polymorphismen im Tumor-Nekrose-Alpha Gen und im Interleukin-10 Gen bei Patienten mit dilatativer Kardiomyopathie. : Philipps-Universität Marburg 2013-06-12. DOI: https://doi.org/10.17192/z2013.0302.
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This item has been published with the following license: In Copyright