Association of Pvull and Xbal polymorphisms on estrogen receptor alpha (ESR1) gene to changes into serum lipid profile of postmenopausal women: Effects of aging, body mass index and breast cancer incidence

作者：Gomes Rochette Neuza Felix; Souza Leticia Soncini; Tommasi Bruno Otoni; Pedrosa Diego Franca; Eis Sergio Ragi; Francischetto Fin Irani Do Carmo; Herkenhoff Vieira Fernando Luiz; Graceli Jones Bernardes; Azevedo Rangel Leticia Batista; Silva Ian Victor^*

来源：PLos One, 2017, 12(2): e0169266.

DOI：10.1371/journal.pone.0169266

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 (Pvull) and c454-351A>G (Xbal) 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 postmenopausal 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 Pvul I SNP on ESR1 gene were observed on patient's serum T-chol, TL, LDL, HDL, and TG. However, c454-397T>C Pvull 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 Xbal 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 Xbal c454351A>G on ESR1 gene is enhanced in both obese (higher BMI) and elder women. Taken together, these results suggested that Xbal 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.

• 出版日期2017-2-15