title: Association of PvuII and XbaI polymorphisms on estrogen receptor alpha (ESR1) gene to changes into serum lipid profile of post-menopausal women: Effects of aging, body mass index and breast cancer incidence.
abstract: Estrogen is a steroidal hormone involved in several physiological functions in the female body including regulation of serum lipid metabolism and breast cancer (BC). Estrogen actions on serum lipids mostly occur through its binding to intracellular Estrogen Receptor alpha (ERalpha) isoform, expressed in most of tissues. This gene (ESR1) exhibit many polymorphic sites (SNPs) located either on translated and non-translated regions that regulate ERalpha protein expression and function. This paper aimed to investigate the association of two intronic SNPs of ESR1 gene, namely c454-397T>C (PvuII) and c454-351A>G (XbaI) to alterations in serum levels of total cholesterol (T-chol), total lipid (TL), low density lipoprotein cholesterol (LDL), high density lipoprotein (HDL), and triglycerides (TG) in a cohort of post-menopausal women. In addition, we aimed to associate presence of these SNPs to development of BC along 5 years period. To do so, a group of healthy 499, highly miscigenated, post-menopausal Brazilian women, were carried using PCR-FRLP technique and further confirmed by automatic sequence analysis as well followed through 5 years for BC incidence. Measurements of serum lipid profile by standard commercial methods were carried individually whereas Dual Energy X-ray Absorciometry (DXA) measured Body Mass Indexes (BMI), Fat Mass (FM), Lean Body Mass (LBM), and Body Water Content (BWC). No effects of PvuII SNP on ESR1 gene were observed on patient´s serum T-chol, TL, LDL, HDL, and TG. However, c454-397T>C PvuII SNP is associated to lower body fat and higher levels of lean mass and body water and lower incidence of BC. On the other hand, statistically significant effect of XbaI c454-351A>G SNP on serum TG and TL levels. Patients homozygous for X allele were followed up from 2010-2015. They showed higher incidence of breast cancer (BC) when compared to either heterozygous and any P allele combination. Moreover, the increasing of TG and TL serum concentrations associated to SNP XbaI c454-351A>G on ESR1 gene is enhanced in both obese (higher BMI) and elder women. Taken together, these results suggested that XbaI c454-351A>G SNP is associated to changes in lipid profile, particularly in serum TG and TL, in this cohort of post-menopausal woman. Also, this paper shows another link between obesity and BC corroborating the current thesis that both diseases are interlinked.
authors.affiliation: Aging Cell Biology Laboratory, Morphology Department, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.|Programa de Pós-Graduação em Biotecnologia/RENORBIO, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.
authors.forename: Neuza Felix
authors.initials: NF
authors.lastname: Gomes-Rochette
authors.affiliation: Aging Cell Biology Laboratory, Morphology Department, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.|Programa de Pós-Graduação em Biotecnologia/RENORBIO, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.
authors.forename: Letícia Soncini
authors.initials: LS
authors.lastname: Souza
authors.affiliation: Instituto Tommasi de Pesquisa e Desenvolvimento, Vila Velha, Espírito Santo, Brazil.
authors.forename: Bruno Otoni
authors.initials: BO
authors.lastname: Tommasi
authors.affiliation: Aging Cell Biology Laboratory, Morphology Department, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.|Programa de Pós-Graduação em Biotecnologia/RENORBIO, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.
authors.forename: Diego França
authors.initials: DF
authors.lastname: Pedrosa
authors.affiliation: Centro de Diagnóstico e Pesquisa da Osteoporose do Espírito Santo-CEDOES, Vitória, Espírito Santo, Brazil.
authors.forename: Sérgio Ragi
authors.initials: SR
authors.lastname: Eis
authors.affiliation: Centro de Diagnóstico e Pesquisa da Osteoporose do Espírito Santo-CEDOES, Vitória, Espírito Santo, Brazil.
authors.forename: Irani do Carmo Francischetto
authors.initials: ID
authors.lastname: Fin
authors.affiliation: Aging Cell Biology Laboratory, Morphology Department, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.
authors.forename: Fernando Luiz Herkenhoff
authors.initials: FL
authors.lastname: Vieira
authors.affiliation: Aging Cell Biology Laboratory, Morphology Department, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.|Programa de Pós-Graduação em Biotecnologia/RENORBIO, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.|Laboratory of Endocrinology and Cellular Toxicology, Programa de Pós-Graduação em Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.
authors.forename: Jones Bernardes
authors.initials: JB
authors.lastname: Graceli
authors.affiliation: Aging Cell Biology Laboratory, Morphology Department, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.|Programa de Pós-Graduação em Biotecnologia/RENORBIO, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.|Laboratory of Cellular and Molecular Biology of Human Cancer, Pharmaceutical Sciences Department, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.
authors.forename: Letícia Batista Azevedo
authors.initials: LB
authors.lastname: Rangel
authors.affiliation: Aging Cell Biology Laboratory, Morphology Department, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.|Programa de Pós-Graduação em Biotecnologia/RENORBIO, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.
authors.forename: Ian Victor
authors.initials: IV
authors.lastname: Silva
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics; D015252:Deoxyribonucleases, Type II Site-Specific; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D015994:Incidence; D008055:Lipids / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000097:blood / Q000235:genetics
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D008055:Lipids; C025580:endodeoxyribonuclease XBAI; D015252:Deoxyribonucleases, Type II Site-Specific