Assoziationsanalysen im TGFA- und TGFB3-Gen bei Patienten mit Lippen-Kiefer-Gaumenspalten und Gaumenspalten

Nicht syndromale Lippen-Kiefer-Spalten mit oder ohne Gaumenspalte (LK/GS) und isolierte Gaumenspalten (GS) gehören zu den häufigsten angeborenen Fehlbildungen des Menschen. Bisher ist über die Ätiologie sehr wenig bekannt. Man geht davon aus, dass es sich um eine multifaktorielle Genese handelt, bei...

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Bibliographic Details
Main Author: Pletsch, Nadine
Contributors: Koch, Manuela (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2003
Online Access:PDF Full Text
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Non-syndromic cleft lips with or without cleft palate (CL/P) and cleft palates only (CPO) are one of the most common disorders estimated to occur in 1:700- 1:1000 live births as a result of a combination of genetic and environmental factors. Association studies of CL/P identified a number of candidate genes but proved to be difficult to reproduce. Here we wish to report our results investigating the two candidate genes TGFA and TGFB3 for the german CL/P population. Our case-control study of 37 patients displaying CL/P showed the rare allele 4bp of the polymorphism wt->4bp located at TGFA to be associated with CL/P (P=0.02). To circumvent effects of the populationstratification a family based association study (TDT) was carried out confirming the significant association (P=0.04). Earlier studies carried out in the US american population did show this association as well. Therefore, the rare allele 4bp can be viewed as a modifier gene in CL/P. Biological support for a role of TGFA arises from its presence at high levels in the epithilial tissue of the medial edge of the palatale shelves at the time of fusion in mice.