Human Molecular Genetics Advance Access published online on July 13, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi242
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Center for Cancer Research, E17-536, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
* To whom correspondence should be addressed. High levels of small low-density lipoprotein (LDL) particles are a major risk factor for cardiovascular morbidity and mortality. Both estrogens and smoking, with known anti-estrogenic effects, alter the atherogenic lipid profile. We tested for a role of interaction between smoking and estrogen receptor
Received February 26, 2005
Revised July 1, 2005
Accepted July 1, 2005
Article
Tobacco smoking, estrogen receptor
gene variation, and small low-density lipoprotein level
2 the Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA
3 Biostatistics Research Center, Institute of Clinical Research and Health Policy Studies, Tufts-New England Medical Center, Boston, Massachusetts 02111, USA
4 Nutrition and Genomics Laboratory, USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111, USA
5 Molecular Cardiology Research Institute, Department of Medicine, New England Medical Center, Boston, Massachusetts 02111, USA and the Tufts-New England Medical Center Specialized Centre of Research in Ischemic Heart Disease.
6 Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Amanda M. Shearman, E-mail: shearman{at}mit.edu
Abstract 
gene (ESR1) variation in association with plasma concentration of atherogenic small LDL particles and LDL particle size. We studied 1727 unrelated subjects, 854 women and 873 men, mean age 51 years (SD 10), from the population based Framingham Heart Study. After covariate adjustment women who smoked and had the common ESR1 c.454-397 TT genotype (in 30% of women T was present on both chromosomes at position 397 prior to the start of exon 2) had > 1.7-fold higher levels of small LDL particles than women with the alternative genotypes (P for smoking-genotype interaction = 0.001). Similar results were obtained for three other ESR1 variants, including c.454-351A>G, in the same linkage disequilibrium block. A similar substantial gender-specific result was also evident with a fifth variant, in a separate linkage disequilibrium block, in exon 4 (P = 0.003). Women who smoked and had specific, common ESR1 genotypes had a substantially higher plasma concentration of atherogenic small LDL particles. Significant results revealed a dose dependent effect of smoking, and were evident in both pre- and postmenopausal women. The reported association has the potential to explain the risks associated with estrogen use in certain women and a recent report of association between an ESR1 haplotype composed of c.454-397 T and c.454-351 A alleles with increased myocardial infarction and ischemic heart disease, independent of the standard, established cardiovascular risk factors.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. L. E. Klos, E. Boerwinkle, R. E. Ferrell, S. T. Turner, and A. C. Morrison ESR1 polymorphism is associated with plasma lipid and apolipoprotein levels in Caucasians of the Rochester Family Heart Study J. Lipid Res., August 1, 2008; 49(8): 1701 - 1706. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Peter, A. Kelley-Hedgepeth, C. S. Fox, L. Adrienne Cupples, G. S. Huggins, D. E. Housman, R. H. Karas, M. E. Mendelsohn, D. Levy, and J. M. Murabito Variation in Estrogen-Related Genes Associated with Cardiovascular Phenotypes and Circulating Estradiol, Testosterone, and Dehydroepiandrosterone Sulfate Levels J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2779 - 2785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Gallagher, C. D. Langefeld, C. J. Gordon, J. K. Campbell, J. C. Mychalecky, M. Bryer-Ash, S. S. Rich, D. W. Bowden, and M. M. Sale Association of the Estrogen Receptor-{alpha} Gene With the Metabolic Syndrome and Its Component Traits in African-American Families: The Insulin Resistance Atherosclerosis Family Study Diabetes, August 1, 2007; 56(8): 2135 - 2141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Peter, G. S. Huggins, A. M. Shearman, A. Pollak, C. H. Schmid, L. A. Cupples, S. Demissie, R. D. Patten, R. H. Karas, D. E. Housman, et al. Age-Related Changes in Echocardiographic Measurements: Association With Variation in the Estrogen Receptor-{alpha} Gene Hypertension, May 1, 2007; 49(5): 1000 - 1006. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Alevizaki, K Saltiki, A Cimponeriu, I Kanakakis, N Xita, C C Alevizaki, I Georgiou, and H-L Sarika Severity of cardiovascular disease in postmenopausal women: associations with common estrogen receptor {alpha} polymorphic variants Eur. J. Endocrinol., April 1, 2007; 156(4): 489 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Gallagher, K. L. Keene, J. C. Mychaleckyj, C. D. Langefeld, J. N. Hirschhorn, B. E. Henderson, C. J. Gordon, B. I. Freedman, S. S. Rich, D. W. Bowden, et al. Investigation of the Estrogen Receptor-{alpha} Gene With Type 2 Diabetes and/or Nephropathy in African-American and European-American Populations Diabetes, March 1, 2007; 56(3): 675 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Lawlor, N. Timpson, S. Ebrahim, I. N.M. Day, and G. D. Smith The association of oestrogen receptor {alpha}-haplotypes with cardiovascular risk factors in the British Women's Heart and Health Study Eur. Heart J., July 1, 2006; 27(13): 1597 - 1604. [Abstract] [Full Text] [PDF]
|
|