Document Detail


Estrogen receptor genotypes, menopausal status, and the effects of tamoxifen on lipid levels: revised and updated results.
MedLine Citation:
PMID:  20827267     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously reported that the ESR1 XbaI genotypes were associated with baseline and tamoxifen-induced serum lipid profiles. The analysis in that study was carried out by PCR followed by restriction-enzyme digestion. After reanalysis using more robust TaqMan assays, the findings related to ~10% of the genotypes for the ESR1 XbaI single-nucleotide polymorphism (SNP) were revised. For the other genotypes (i.e., ESR1 PvuII, ESR2, and CYP2D6), the results were nearly identical to those in the previous study. Upon reanalysis, previously reported associations between the ESR1 Xba1 genotypes and baseline triglyceride and low-density lipoprotein (LDL) cholesterol levels were no longer observed. Previously reported associations between the ESR1 XbaI genotypes and tamoxifen-induced changes in levels of total cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol were also no longer observed. However, the following observations from the original report did not change: (i) the levels of circulating lipids are lower in women taking tamoxifen; (ii) there is an association between the ESR2-02 genotypes and changes in triglyceride levels; and (iii) neither ESR1 PvuII nor CYP2D6 is associated with any changes in serum lipid concentrations in patients receiving treatment with tamoxifen.
Authors:
D F Hayes; T C Skaar; J M Rae; N L Henry; A T Nguyen; V Stearns; L Li; S Philips; Z Desta; D A Flockhart;
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-09-08
Journal Detail:
Title:  Clinical pharmacology and therapeutics     Volume:  88     ISSN:  1532-6535     ISO Abbreviation:  Clin. Pharmacol. Ther.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-20     Completed Date:  2010-11-08     Revised Date:  2011-04-21    
Medline Journal Info:
Nlm Unique ID:  0372741     Medline TA:  Clin Pharmacol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  626-9     Citation Subset:  AIM; IM    
Affiliation:
Department of Internal Medicine and Breast Oncology Program, Comprehensive Cancer Center, University of Michigan Health and Hospitals System, Ann Arbor, Michigan, USA. hayesdf@umich.edu
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00228930
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MeSH Terms
Descriptor/Qualifier:
Breast Neoplasms / blood,  drug therapy*,  genetics
Cholesterol / blood
Cholesterol, HDL / blood
Cholesterol, LDL / blood
Cytochrome P-450 CYP2D6 / genetics
Estrogen Receptor alpha / genetics*
Estrogen Receptor beta / genetics*
Female
Genotype
Humans
Lipids / blood*
Phenotype
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Polymorphism, Single Nucleotide*
Postmenopause*
Premenopause*
Reproducibility of Results
Selective Estrogen Receptor Modulators / therapeutic use*
Tamoxifen / therapeutic use*
Time Factors
Treatment Outcome
Triglycerides / blood
Grant Support
ID/Acronym/Agency:
M01-RR00042/RR/NCRR NIH HHS; M01RR00750/RR/NCRR NIH HHS; U-01 GM61373/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Cholesterol, HDL; 0/Cholesterol, LDL; 0/Estrogen Receptor alpha; 0/Estrogen Receptor beta; 0/Lipids; 0/Selective Estrogen Receptor Modulators; 0/Triglycerides; 0/estrogen receptor alpha, human; 10540-29-1/Tamoxifen; 57-88-5/Cholesterol; EC 1.14.14.1/Cytochrome P-450 CYP2D6

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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