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

Pharmacogenet Genomics. 2006 May;16(5):379-83. doi: 10.1097/01.fpc.0000204996.76559.d0.

Abstract

Objective: Information on single nucleotide polymorphisms in the estrogen receptor beta (ERbeta) gene is lacking for the African American population.

Methods: In this study, we systematically screened the coding and flanking intron regions of the ERbeta 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 ERbetaF289L. This receptor variant was characterized in vitro for transcriptional activity and ligand-binding. These studies revealed that ERbetaF289L had reduced estrogen binding affinity and impaired response to 17beta-estradiol induced transactivation compared to the wild-type ERbeta.

Conclusion: This novel variant might confer genetic susceptibility to certain endocrine related diseases in African Americans.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Substitution
  • Black or African American / genetics*
  • DNA / genetics*
  • Dose-Response Relationship, Drug
  • Estradiol / pharmacology
  • Estrogen Receptor beta / genetics*
  • Estrogen Receptor beta / metabolism*
  • Genetic Testing*
  • Genetic Variation*
  • Humans
  • In Vitro Techniques
  • Leucine / metabolism
  • Ligands
  • Transcription, Genetic
  • Transcriptional Activation

Substances

  • Estrogen Receptor beta
  • Ligands
  • Estradiol
  • DNA
  • Leucine