Characterization of DNA polymorphisms in the E-cadherin gene (CDH1) promoter region.

E-cadherin is a tumor suppressor involved in epithelial cell-cell interactions. Some of the nucleotide variation in the 5'-promoter region of the gene influences transcriptional efficiency. We investigated single nucleotide polymorphisms (SNPs) in the promoter-exon 1 region of the E-cadherin gene (CDH1) using fluorescence-based PCR-single-strand conformation polymorphism (PCR-SSCP) analysis. We detected four kinds of polymorphisms between nucleotides -516 and +12, numbering from the translation initiation site. SNPs were localized at -472G-->GA, -288T-->deltaT, -285C-->A, and -54G-->C. Variants -472GA and -285A were frequently found in controls, but the -288deltaT and -54C are rare variants. We examined the effects of these variants on transcription. The activity of promoters containing the variants -288deltaT, -285A, or -54C was lower than the activity of promoters with the major variants, as assayed by a luciferase reporter gene. Variants -472G and -472GA displayed the same promoter activity. The decreased transcriptional activity from variant promoters affects the expression of E-cadherin.