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

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.