Functional characterization of a novel variant of estrogen receptor beta identified in screening of DNA derived from African Americans

Objective: Information on single nucleotide polymorphisms in the estrogen receptor beta (ERβ) gene is lacking for the African American population. Methods: In this study, we systematically screened the coding and flanking intron regions of the ERβ gene in 49 healthy African American individuals. Results: We detected four novel variants, of which one variant (963T→C) resulted in amino acid change from phenylalanine to leucine at position 289, referred to as ERβF289L. This receptor variant was characterized in vitro for transcriptional activity and ligand-binding. These studies revealed that ERβF289L had reduced estrogen binding affinity and impaired response to 17β-estradiol induced transactivation compared to the wild-type ERβ. Conclusion: This novel variant might confer genetic susceptibility to certain endocrine related diseases in African Americans.