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Identification of germline genetic variations in the 5' region of the estrogen receptor beta gene
Author(s) -
Philips S.,
Bermes A.,
Nguyen A. T.,
Luzcando R.,
Narayanan P. B.,
Flockhart D. A.,
Skaar T. C.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.131
Subject(s) - single nucleotide polymorphism , biology , genetics , estrogen receptor alpha , intron , exon , gene , estrogen receptor , promoter , tamoxifen , germline , tata box , snp , genotype , gene expression , cancer , breast cancer
Background Tamoxifen therapy causes variable phenotypic effects on target tissues. Currently, there is no way to predict which patients will have beneficial or harmful side effects from it. Germline genetic polymorphisms in the estrogen receptors (ERs) are associated with altered responses to estrogenic therapies and baseline parameters (e.g. bone mineral density and serum lipids). Little information is available on the germline genetic variations in the estrogen receptor beta (ERβ) gene. We hypothesize that genetic variations in the ERs may account for part of the variability in the tamoxifen induced side effects. The aim of this study was to identify genetic polymorphisms in the promoter of the ERβ gene. Methods Using a bioinformatic approach, we compared the promoter sequences of the human, chimpanzee, rat and mouse ERβ genes. We found a region of strong homology immediately upstream of the exon 0N. This region has also been shown to be a site of in vivo methylation. Therefore, we resequenced approximately 1.6 kb of the ERβ promoter, exon 0N and intron 1 in 50 African‐American (AA) and 50 Caucasian (Cau) subjects. Results In AA samples, we found 5 single nucleotide polymorphisms (SNPs) in the promoter, one of which altered the predicted TATA box in the promoter. We also found a SNP in intron 1 that was observed in both Cau and AA. There were no SNPs detected in the exon 0N. Conclusion The promoter of the ERβ gene contains at least one SNP that may alter its transcriptional activity and tamoxifen responses. Clinical Pharmacology & Therapeutics (2005) 77 , P63–P63; doi: 10.1016/j.clpt.2004.12.131