Transforming growth factor-alpha: characterization of the BamHI, RsaI, and TaqI polymorphic regions

We have characterized the nature of structural alleles of the transforming growth factor-alpha (TGF alpha) locus by restriction-enzyme digestion with BamHI, RsaI, and TaqI. The BamHI polymorphic site is located within exon VI, which codes for the 3' untranslated region. The two BamHI alleles differ by a single point mutation at the restriction site. The RsaI and TaqI polymorphic sites are located within intron V. The two alleles differ at the restriction site, either by a point mutation (RsaI) or by a 4-bp deletion (TaqI). This analysis permits us to devise a PCR method coupled with restriction digestions to directly identify the TGF alpha polymorphisms. Analysis of 99 Caucasian controls has revealed a highly significant (P < .001) association between the RsaI and the BamHI genotype. The frequency of the rare BamHI allele was significantly higher (P < .001) in transformed cell lines (.30) than in controls (.076).