Background: The present study represents the first attempt to functionally characterize two common single nucleotide polymorphisms (SNPs) in the 3'untranslated regions (3'UTRs) of estrogen receptor beta (ERbeta), focusing on the differences between alleles with regard to mRNA stability and translatability. These two ERbeta SNPs have been investigated for association with disease in a large number of reports.
Results: Here we examined allelic expression in breast tumor samples from heterozygous individuals. A significant difference in mRNA levels of the two alleles was observed for one of the SNPs. A cell model system was employed to further investigate potential molecular effects of the two SNPs. We used a modified plasmid, containing the ERbeta promoter and ERbeta 3'UTRs which include the different alleles of investigated SNPs. Quantitative Real-Time PCR was used to determine mRNA levels after inhibition of transcription by actinomycin D, and a luciferase assay was used to determine protein levels. The obtained results suggested that there was no difference in mRNA stability or translatability between the alleles of investigated SNPs.
Conclusion: Our results indicate that observed associations between ERbeta 3'UTR SNPs and disease susceptibility are due to linkage disequilibrium with another gene variant, rather than the variant itself being the susceptibility factor.