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.
Subject(s)
Body Mass Index , Breast Neoplasms , Estrogen Receptor alpha/genetics , Lipids/blood , Obesity , Polymorphism, Single Nucleotide , Postmenopause , Aged , Aged, 80 and over , Aging , Breast Neoplasms/blood , Breast Neoplasms/genetics , Deoxyribonucleases, Type II Site-Specific , Estrogen Receptor alpha/metabolism , Female , Humans , Incidence , Lipids/genetics , Middle Aged , Obesity/blood , Obesity/genetics , Postmenopause/blood , Postmenopause/geneticsABSTRACT
The aim of this work was to study the estrogen receptor alpha (ERS1) PvuII and XbaI gene polymorphisms prevalence in randomly selected women population from Rio de Janeiro and Espírito Santo states in Brazil by polymerase chain reaction restriction fragment lengths polymorphism (PCR_RFLP) methodology. It was shown that Rio de Janeiro women exhibited a significantly different prevalence of XbaI polymorphism comparing to Espirito Santo women. Nonetheless, similar prevalence of PvuII polymorphism was found in both women´s populations. Moreover, a strong linkage disequilibrium was observed between these SNPs reinforcing the hypothesis of differential pattern of inheritance observed on such populations.
ABSTRACT
OBJECTIVE: To evaluate the association of -397T>C and -351A>G single nucleotide polymorphisms (SNPs) - also called PvuII and XbaI, respectively - located on estrogen receptor alpha (ERS1) gene with age at menarche, menopause onset, fertility and miscarriage in a population of post-menopausal women. STUDY DESIGN: Cross-sectional study with 273 healthy, high miscegenated, post-menopausal women (mean age of 63.1±9.7 years old). Subjects were genotyped for PvuII and XbaI SNPs by PCR-RFLP and confirmed by automatic sequencing. Reproduction informations (age at menarche, age at menopause, number of pregnancies, fertility rate and miscarriages) were obtained by retrospective study using a questionnaire. RESULT(S): Age at menarche, menopause onset, number of pregnancies, total fertility rate, and parity did not seem to be influenced by any of the studied genotypes (chi-square, p>0.05). However, women carrying the xx genotype showed a 44% higher chance of miscarriage, whereas this value did not trespass 16% for any other genotype analyzed. It has been also observed a higher occurrence of miscarriage in association with combined xxpp genotype of ERS1 gene (chi-square, p<0.01). CONCLUSION(S): The present data indicate that the studied SNPs on ERS1 gene do not influence the menstrual cycle timing and parity but there is a strong relationship between the xx ERS1 SNP genotype and the incidence of miscarriage in the post-menopausal population analyzed.
Subject(s)
Abortion, Spontaneous/genetics , Estrogen Receptor alpha/genetics , Polymorphism, Single Nucleotide , Age Factors , Aged , Chi-Square Distribution , Cross-Sectional Studies , Female , Fertility/genetics , Genotype , Humans , Menarche/genetics , Menopause/genetics , Middle Aged , Parity/genetics , Postmenopause , PregnancyABSTRACT
O caranguejo-uçá (Ucides cordatus) é um crustáceo (Decápoda: Brachyura) de grande valor cultural, biológico e comercial em todo Espírito Santo. Contudo, ainda há uma grande lacuna de conhecimentos acerca de sua biologia. Com o intuito de minimizar essa carência, o presente trabalho realizou um estudo sobre a caracterização morfológica de três populações do caranguejo-uçá (Ucides cordatus L.) em manguezais do Espírito Santo. Foram analisadas quatro características morfométricas em 172 indivíduos machos, coletados nas cidades de São Mateus (N=62), Vitória (N=60) e Anchieta (50). Foi observada diferença significativa entre as três populações (p<0,01) por meio de uma Análise de Variância Multivariada. O maior grau de similaridade foi encontrado entre as populações de São Mateus (Norte) e Anchieta (Sul), de modo que a população de Vitória (Centro) foi agrupada separadamente, evidenciando-se divergência entre essa população e as demais. Os resultados sugerem pressões de seleção diferentes nas populações do interior em relação à população da capital, o que pode estar relacionado a uma maior ação antrópica nas populações da capital.
