Einfluss von „single nucleotide polymorphisms“ der Hitzeschockproteine HSPA1L und HSPA1B sowie der Zytokine IL6, IL10, TNF-α und TNF-β auf die Entstehung der Herzinsuffizienz bei Patienten mit 3-Gefäß-KHK

Die pathophysiologischen Zusammenhänge in der Entwicklung der chronischen Herzinsuffizienz sind komplex und im Einzelnen noch nicht verstanden. In den letzten Jahren konnte gezeigt werden, dass Entzündungsprozesse neben neurohormonalen und hämodynamischen Anpassungsvorgängen und der Bedeutung von fr...

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Bibliographic Details
Main Author: Kliebe, Frank
Contributors: Maisch, Bernhard (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2007
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Background. Cytokines and heat shock proteins play an important role in the pathogenesis of coronary artery disease and heart failure. Functional single nucleotide polymorphisms (SNP´s) in the genes of IL6 (-174C/G), IL10 (-819C/T; -1082A/G), TNF-α (-308G/A) and TNF-β (+252A/G) are associated with variable gene expressions and plasma level of the cytokines. The gene expression of HSPA1B (+1267G/A) is also influenced by SNP´s. In HSPA1L (+2437T/C) a SNP causes an Met-Thr aminoacid-substitution whithin the proposed peptide binding site of HSPA1L. The aim of the study was to investigate the potential association of the polymorphisms and the development of heart failure in patients with 3-vessel-coronary artery disease (CAD). Methods. We compared two groups of angiographically examined patients with 3-vessel CAD. One Group (n=82) had symptoms and signs of heart failure, second group (n=82) did not. The groups were matched for age, sex, risk factors for CAD and other diseases which may cause or influence heart failure. DNA extracted from peripheral blood of the 164 patients was amplified by polymerase chain reaction for 5 cytokine-SNP´s and 2 HSP-SNP´s. The genotypes were resolved by gel electrophoresis after restriction enzyme digestion. We used the Cochran-Armitage-Trend-Test for statistical analysis. Results. We did not find a significant difference of allele frequency between the two groups for IL6 (p=0.592), IL10 (p=0.29; p=0.713), TNF-α (p=0.277), TNF-β (p=0.308) and HSPA1B (p=0.182). For HSPA1L we found a significant difference (p=0.023) of allele frequency between group 1 (8.5%) and group 2 (0%). Conclusions. The HSPA1L +2437CC-genotype causes an Met-Thr-aminoacid-substitution within the peptide binding site of the proteine. This may influence the peptide binding specifity and the protective function of HSPA1L. Therefor our data demonstrate a possible influence of the HSPA1L +2437T/C-polymorphism to the development of heart failure in patients with 3-vessel-CAD.