Functional analysis of human ornithine decarboxylase alleles

It has been known for >10 years that there are two alleles of the human orn ithine decarboxylase (ODC) gene, defined by a polymorphic PstI RFLP in intr on 1, We have sequenced a large portion of each of the two alleles, includi ng some of the 5' promoter region, exon 1, intron 1, and exon 2, and determ ined that a single nucleotide polymorphism at base +317 (relative to transc ription start site) Is responsible for the presence or absence of the PstI restriction site. We have developed two genotyping assays, a PCR-RFLP assay and a high-throughput TaqMan-based method, and determined the ODC genotype distribution in >900 North American DNA samples. On the basis of its locat ion between two closely spaced Myc/Max binding sites (E-boxes), we speculat ed that the single nucleotide polymorphism at base +317 could have function al significance, Results of transfection assays with allele-specific report er constructs support this hypothesis, The promoter/regulatory region deriv ed from the minor ODC allele (A allele) was more effective in driving lucif erase expression in these assays than the identical region from the major a llele (G allele), Our results suggest that individuals homozygous for the A allele may be capable of greater ODC expression after environmental exposu res, especially those that up-regulate c-MYC expression.