title: Identification of a functional variant of estrogen receptor beta in an African population.
abstract: In this study, we identified five novel polymorphisms in the estrogen receptor beta (ERbeta) gene in an African population. Interestingly, two of these variants are expected to change the amino acid sequence of the ERbeta protein. These changes correspond to an isoleucine to valine substitution at amino acid position 3 (I3V) and a valine to glycine substitution at position 320 (V320G), respectively. The functional consequences of these amino acid substitutions were determined in different in vitro assays. The I3V mutation displayed no differences with regard to transcriptional activity in a reporter assay, as compared with the wild-type receptor. The V320G mutation, however, showed significantly decreased maximal transcriptional activity in a reporter assay, although its binding affinity for 17beta-estradiol was not affected. A pull-down assay indicated that the interaction of full-length TIF2 with hERbetaV320G was weaker than with hERbetawt. Moreover, surface plasmon resonance analysis revealed reduced interaction of the V320G ERbeta variant with the NR box I and II modules of TIF2. To our knowledge, this represents the first identification of a functional polymorphism in the ERbeta gene. This novel polymorphism provides a tool for human genetic studies of diseases in the African population.
authors.affiliation: Karolinska Institute, Department of Biosciences at Novum, S-141 57 Huddinge, Sweden.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Michio
authors.initials: M
authors.lastname: Otsuki
authors.forename: Gudrun
authors.initials: G
authors.lastname: Toresson
authors.forename: Konrad
authors.initials: K
authors.lastname: Koehler
authors.forename: Qiang
authors.initials: Q
authors.lastname: Pan-Hammarström
authors.forename: Lennart
authors.initials: L
authors.lastname: Hammarström
authors.forename: Stefan
authors.initials: S
authors.lastname: Nilsson
authors.forename: Jan-Ake
authors.initials: JA
authors.lastname: Gustafsson
authors.forename: Karin
authors.initials: K
authors.lastname: Dahlman-Wright
mesh_terms: D000595:Amino Acid Sequence; D044383:Black People / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D047629:Estrogen Receptor beta / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D009549:Nigeria; D010446:Peptide Fragments / Q000737:chemistry; D010957:Plasmids; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011487:Protein Conformation; D013548:Sweden; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D047629:Estrogen Receptor beta; D010446:Peptide Fragments