Dokument

Zusammenfassung:
Bei der Pathogenese der DCM sind diverse Zytokine beteiligt. In diesem Kontext spielen insbesondere das pro-inflammatorische TNF-α und das anti-inflammatorische IL-10 eine wichtige Rolle. In der Literatur wurde über einen Zusammenhang des G/A-SNP am Genlocus -308 im TNF-α Gen und des G/A-SNP am Genlocus -1082 im IL-10 Gen mit einer DCM berichtet. In der eigenen Untersuchung wurde in einer Patientengruppe, welche sich aus 421 an der DCM erkrankten Patienten zusammensetzte, und einer aus 374 gesunden Personen bestehenden Kontrollgruppe mittels Polymerasekettenreaktion und Restriktionsfregmentlängenpolymorphismusanalyse die Frequenz der o.g. SNPs untersucht und geprüft, ob eine Assoziation des -308 G/A-SNP im TNF-α Gen und des -1082 G/A-SNP im IL-10 Gen mit einer DCM besteht. Des Weiteren wurde in einer aus 153 Patienten bestehenden Patientengruppe untersucht, ob die o.g. SNP mit den klinischen Charakteristika wie EF, SF, EDP, HF, LVEDD oder EDVI assoziiert sind. Ebenfalls wurde überprüft, ob eine Assoziation der o.g. SNP zum PB19 oder einer fDCM besteht. Die Frequenz des TNFA2-Allels war in der Patientengruppe signifikant höher als in der Kontrollgruppe (27,94% vs 22,06%, p=0,008). Das Vorhandensein eines TNFA2-Allels bedingt eine 1,37-fache Erhöhung des Erkrankungsrisikos an einer DCM (OR=1,37, 95%-KI=1,089/1,724).Weiterhin besteht eine signifikante Assoziation des -308 A/G-Genotyps gegenüber dem -308 G/G-Genotypen mit einer DCM (p=0,001). Der -308 A/A-Genotyp ist demgegenüber nicht mit einer DCM assoziiert. Es besteht außerdem keine Assoziation des -308 G/A-SNP mit den klinischen Charakteristika in der Indexpatientengruppe. Auch existiert keine Assoziation des o.g. SNP mit einer fDCM oder der Präsenz des Parvovirus B19. Weder IL-10*1A (p=0,81) noch der -1082 A/G- oder der A/A-Genotyp (p=0,253) im IL-10 Gen sind mit einer DCM assoziiert. Innerhalb der Indexpatientengruppe ließ sich eine signifikante Assoziation des -1082 A/A-Genotyp mit dem EDP und der LVEDD im Follow-up gegenüber dem A/G-Genotyp nachweisen. Alle anderen untersuchten klinischen Parameter waren nicht mit dem o.g. SNP assoziiert. Die Ergebnisse in der eigenen Arbeit legen einen Zusammenhang des TNFA2-Allels und des -308 TNF-α A/G-Genotyps mit der Pathogenese einer DCM in einer in Deutschland lebenden Gruppe nahe. Der -1082 IL-10 G/A-SNP ist in der eigenen Untersuchung nicht mit der Pathogenese einer DCM assoziiert. Da ein Zusammenhang des EDP und des linksventrikulären enddiastolischen Diameters (LVEDD) im Follow-up mit dem o.g. SNP detektiert wurden, könnte möglicherweise ebenfalls eine Assoziation des -1082 IL-10 G/A-SNP mit einer DCM existieren, welcher in dieser Arbeit nicht erfasst wurde. In nachfolgenden Untersuchungen könnte dieselbigen Analysen noch einmal an einer größeren Patientenzahl durchgeführt werden, um diesem Sachverhalt noch einmal nachzugehen. Da das Vorhandensein eines -308 A-Allels im TNF-α Gen (TNFA2) mit eine erhöhte Sekretion des pro-inflammatorischen Zytokins TNF-α und das Vorliegen eines -1082 A-Allels im IL-10 Gen (IL-10 1A*) mit einer erniedrigten Sekretion des anti-inflammatorischen Zytokins IL-10 assoziiert sind, was wiederum eine Inflammation und die Pathogenese einer DCM triggert, wäre es interessant in weiterführenden Untersuchungen auch die Plasmaspiegel der o.g. Zytokine messen.

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