Identification of a functional variant of estrogen receptor beta in an African population Export

@article{citeulike:3658754, abstract = {In this study, we identified five novel polymorphisms in the estrogen receptor beta (ER{beta}) gene in an African population. Interestingly, two of these variants are expected to change the amino acid sequence of the ER{beta} 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 17{beta}-estradiol was not affected. A pull-down assay indicated that the interaction of full-length TIF2 with hER{beta}V320G was weaker than with hER{beta}wt. Moreover, surface plasmon resonance analysis revealed reduced interaction of the V320G ER{beta} 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 ER{beta} gene. This novel polymorphism provides a tool for human genetic studies of diseases in the African population. 10.1093/carcin/bgh215}, author = {Zhao, Chunyan and Xu, Li and Otsuki, Michio and Toresson, Gudrun and Koehler, Konrad and Pan-Hammarstrom, Qiang and Hammarstrom, Lennart and Nilsson, Stefan and Gustafsson, Jan-Ake and Dahlman-Wright, Karin}, citeulike-article-id = {3658754}, citeulike-linkout-0 = {http://dx.doi.org/10.1093/carcin/bgh215}, citeulike-linkout-1 = {http://carcin.oxfordjournals.org/cgi/content/abstract/25/11/2067}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/15205361}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=15205361}, comment = {The authors describe 5 polymorphisms in the ER-Beta gene - 2 of which are non-synonymous. One of these lowers transcriptional activity.}, doi = {10.1093/carcin/bgh215}, journal = {Carcinogenesis}, keywords = {africa, beta, estrogen-receptor, non-synonymous, polymorphisms}, month = {November}, number = {11}, pages = {2067--2073}, posted-at = {2008-11-22 02:58:39}, priority = {2}, title = {Identification of a functional variant of estrogen receptor beta in an African population}, url = {http://dx.doi.org/10.1093/carcin/bgh215}, volume = {25}, year = {2004} }

TY - JOUR ID - citeulike:3658754 L3 - citeulike-article-id:3658754 N2 - In this study, we identified five novel polymorphisms in the estrogen receptor beta (ER{beta}) gene in an African population. Interestingly, two of these variants are expected to change the amino acid sequence of the ER{beta} 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 17{beta}-estradiol was not affected. A pull-down assay indicated that the interaction of full-length TIF2 with hER{beta}V320G was weaker than with hER{beta}wt. Moreover, surface plasmon resonance analysis revealed reduced interaction of the V320G ER{beta} 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 ER{beta} gene. This novel polymorphism provides a tool for human genetic studies of diseases in the African population. 10.1093/carcin/bgh215 IS - 11 JF - Carcinogenesis EP - 2073 TI - Identification of a functional variant of estrogen receptor beta in an African population VL - 25 SP - 2067 KW - africa KW - beta KW - estrogen-receptor KW - non-synonymous KW - polymorphisms N1 - The authors describe 5 polymorphisms in the ER-Beta gene - 2 of which are non-synonymous. One of these lowers transcriptional activity. AU - Zhao, Chunyan AU - Xu, Li AU - Otsuki, Michio AU - Toresson, Gudrun AU - Koehler, Konrad AU - Pan-Hammarstrom, Qiang AU - Hammarstrom, Lennart AU - Nilsson, Stefan AU - Gustafsson, Jan-Ake AU - Dahlman-Wright, Karin PY - 2004/11/01/ UR - http://dx.doi.org/10.1093/carcin/bgh215 ER -