Estrogen Receptor Alpha Polymorphisms Research Articles

Associations of serum estradiol level, serum estrogen receptor-alpha level, and estrogen receptor-alpha polymorphism with male infertility: A retrospective study.

Estradiol regulates spermatogenesis partly via estrogen receptor-alpha (ESRα). This study aimed to analyze the associations of serum estradiol level, serum ESRα level, and ESRα gene polymorphisms with sperm quality.This retrospective study included infertile men attending the Reproductive Center, Affiliated Hospital of Youjiang Medical University for Nationalities, and a control group without a history of fertility (October, 2016 to March, 2017). Data regarding sperm quality, serum levels of estradiol and ESRα, and rs2234693C/T genotype were extracted from the medical records. Pearson/Spearman correlations (as appropriate) between estradiol level, ESRα level, and sperm quality parameters were evaluated.The analysis included 215 men with infertility and 83 healthy controls. The infertile group had higher serum levels of estradiol (147.57 ± 35.3 vs 129.62 ± 49.11 pg/mL, P < .05) and ESRα (3.02 ± 2.62 vs 1.33 ± 0.56 pg/mL, P < .05) than the control group. For the infertile group, serum estradiol level was negatively correlated with sperm concentration, percentage of progressively motile sperm, and percentage of sperm with normal morphology (r = 0.309, 0.211, and 0.246, respectively; all P < .05). Serum estradiol and ESRα levels were lower in infertile men with normozoospermia than in those with azoospermia, oligozoospermia, mild azoospermia, or malformed spermatozoa (all P < .05). Sperm concentration, percentage of progressively motile sperm, serum ESRα level, and serum estradiol level did not differ significantly among the rs2234693 CC, CT, and TT genotypes.Elevated serum levels of estradiol and possibly ESRα might have a negative impact on sperm quality and fertility, whereas single nucleotide polymorphisms at rs2234693 of the ESRα gene had little or no effect.

Study of Xbal and Pvull polymorphisms of estrogen receptor alpha (ERα) gene in girls with precocious/early puberty.

Studies examining association of estrogen receptor alpha (ERα) polymorphisms with early puberty are scarce and results are controversial; data in Caucasian girls are lacking. Main objective was to determine association of Xbal and Pvull polymorphisms of ERα gene in Greek girls with precocious/early puberty METHODS: We studied 107 girls with idiopathic precocious/early puberty and 81 young women with pubertal maturation within normal age (controls). Pubertal stage, height SDS (HSDS), and BMI z-score were determined in patients. In controls, height was measured and menarcheal age was self-reported. All participants in the study were genotyped for XbaI and PvuII polymorphisms of the ERα gene. There was no significant difference in XbaI and PvuII polymorphisms between patients and controls. Homozygous, xx and pp, girls had an earlier onset of puberty, although non-significant, than heterozygous or with no polymorphisms p = 0.9; in girls with pubertal onset <7 years, the association tended to become significant, p = 0.09. Girls with xxpp genotype were significantly taller, HSDS 1.63, p = 0.014. In controls, homozygosity for Xbal (xx) and PvuII (pp) was associated with significantly earlier menarche than in women with no polymorphism, p = 0.013 and p = 0.026, respectively, and xxpp genotype was associated with taller adult height, p = 0.017. XbaI and PvuII polymorphisms are not related to idiopathic precocious/early puberty. Early pubertal girls homozygous for both polymorphisms presented earlier onset of puberty, although statistically non-significant, and taller height than girls heterozygous or without these polymorphisms. Homozygosity for both polymorphisms is associated with earlier menarche and taller adult height.

Calcium and Phosphorus Levels in Saliva are Influenced by Genetic Polymorphisms in Estrogen Receptor Alpha and Microrna17.

Homeostasis between salivary calcium and phosphorus is important for maintaining oral health. The aim of this study was to evaluate if polymorphisms in ESR1 (Estrogen Receptor Alpha), ESR2 (Estrogen Receptor Beta) and miRNA17 (microRNA17) are associated with calcium and phosphorus levels in saliva. Saliva from 276 12-year-old children were collected by masticatory stimulation and calcium and phosphorus levels were determined by Mass Spectrometry. Genomic DNA was extracted from remaining saliva and genetic polymorphisms in ESR1 (rs12154178, rs1884051, rs9340799 and rs2234693), in ESR2 (rs4986938 and rs1256049) and in miRNA17 (rs4284505) were genotyped using TaqMan chemistry and a real-time PCR equipment. Statistical differences in genotype and allele distributions between 'low' and 'high' calcium and phosphorus levels were determined using chi-square or Fisher´s exact tests. The analysis was also adjusted by sex (alpha of 5%). ESR1 rs9340799 had the less common genotype associated with higher calcium levels (p=0.03). The less common allele of ESR1 rs1884051 was associated with lower phosphorus levels (p=0.005) and there was an excess of heterozygotes for miRNA17 rs4284505 among individuals with lower calcium levels (p=0.002), both adjusted by sex. This study provides evidence that genetic polymorphisms in ESR1 and miRNA17 are involved in determining salivary calcium and phosphorus levels.

Estrogen Receptor Alpha (ERα) Pvu II 397 T/C Related Genotypes and Alleles are Associated with Higher Susceptibilities of Endometriosis

Endometriosis is an estrogen dependent disease that is proved by its development in reproductive age and the decrease after menopause or ovariectomy. Endometriosis characterized by the growth of endometrial outside the uterine cavity, which is found in women with subfertility and pelvic pain problems. Effect of the estrogen hormone depends on the binding to its receptor. Estrogen receptor alpha (ERα) polymorphisms which admit by Pvu II enzyme restriction has associate to some women’s disease like endometriosis. This Study aimed to determine the correlation between ERα 397 T/C with the risk of endometriosis. There were 70 samples which were divided into 2 groups: 35 cases (endometriosis group) and 35 controls (non-endometriosis group). The determination of genotypes and allotypes used PCR-RFLP method and the data analysis by chi square test α<0,05.The results showed that genotype frequencies of case group are 11,4% TT, 54,3% TC and 12% CC while genotype of control group are 34,3% TT, 51,4% TC and 14,3% CC with p value 0,032. Allele frequencies of case group are 38,6% T and 61,4% C while control group are 60% T and 40% C with p value 0,011. Conclusion: there is a significant correlation between the genotype and allele polymorphism of ERα gene 397 T/C with the risk of endometriosis.

Association between Common Genetic Variants in ESR1 and Stroke Risk: A Systematic Review and Meta-Analysis

Objectives: The associations between estrogen receptor alpha (ESR1) polymorphisms and stroke risk have been investigated in various studies, but remain controversial. The aim of this meta-analysis was to determine the relationships between ESR1 rs2234693 and rs9340799 polymorphisms and the risk of stroke. Methods: Electronic databases of PubMed, Embase, Cochrane Library, CNKI, VIP database, and WanFang database were searched for eligible studies up to March 2019. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of associations under different genetic models. Results: Ten independent case-control studies including 2151 stroke cases and 6378 control subjects were enrolled in this meta-analysis. The meta-analysis results indicated that ESR1 rs2234693 polymorphism was associated with an increased risk of stroke in recessive model (OR, 1.20; 95%CI, 1.04-1.38) and homozygous model (OR, 1.18; 95%CI, 1.00-1.38). Subgroup analysis on stroke subtype showed that rs2234693 polymorphism was connected with ischemic stroke, but not hemorrhagic stroke. The further subgroup analyses on ethnicity and gender suggested that the association between rs2234693 polymorphism and stroke risk was significant in Caucasian population and in the male population. No positive associations between rs9340799 polymorphism and stroke risk were detected in 4 genetic models. Conclusions: The results of this meta-analysis suggest that ESR1 rs2234693 polymorphism is significantly correlated with an increased risk of stroke, especially ischemic stroke. There was no evidence of a significant association between ESR1 rs9340799 polymorphism and stroke risk.

Association between gender, estrogen receptors genes and anxiety levels in patients undergoing orthognathic surgery

Orthognathic surgery is a procedure that is performed for the correction of dentofacial deformities and can lead to a change in an individual's anxiety levels. Anxiety is a multifactorial condition in which hormones and genes play an important role. This study aimed to evaluate if gender and genetic polymorphisms in estrogen receptor alpha (ESR1) and beta (ESR2) are associated with anxiety levels in patients undergoing orthognathic surgery. In this longitudinal observational study, 44 patients were included. Anxiety level assessments were performed at three time periods: 2 days before the surgical procedure and 1 and 6 months postoperatively, using the State-Trait Anxiety Inventory Scale. Gender, age, and facial profile were also evaluated. Additionally, a saliva sample from each individual was collected for the genotypic evaluation of ESR1 (rs2234693 and rs9340799) and ESR2 (rs1256049 and rs4986938) using real time polymerase chain reaction. Data were analyzed with a significance level of 0.05. There was a decrease in trait-anxiety and state-anxiety when comparing the preoperative measurements with those obtained 1 and 6 months postoperatively (p < 0.05). Females were more anxious than males at each time point during the study (p < 0.05). The genetic polymorphism rs9340799 in ESR1 was associated with state-anxiety during the preoperative period (p = 0.046). In conclusion, an individual's gender and genetic polymorphism in ESR1 are associated with anxiety in orthognathic surgery patients.

Association of genetic polymorphisms of estrogen and progesterone receptors and endometriosis: Meta-analysis

Purpose: To investigate the association between polymorphisms in the genes of estrogen receptor alpha, estrogen receptor beta, and progesterone receptor and the genesis of endometriosis. Methods: Systematic review and meta-analysis of articles published fully in the PubMed database, in Portuguese, English, or Spanish, from 2006 to 2017, using the descriptors: “endometriosis,” “polymorphism,” “ESR1,” “ESR2,” “PROGINS,” “rs9340799,” “rs4986938,” and “rs1042838.” Results: A total of 20 studies were included based on the criterion of search for susceptibility to endometriosis related to polymorphisms of estrogen receptor alpha, estrogen receptor beta, and progesterone receptor genes. Analysis of all polymorphisms found no association with endometriosis. Conclusion: This meta-analysis showed that estrogen receptor alpha, estrogen receptor beta, and progesterone receptor polymorphisms are not related to susceptibility to endometriosis. However, such results may be able to provide more detailed interpretations of how they influence the pathogenesis of endometriosis.

Influence of Estrogen Receptor Alpha Polymorphism on Bone Mineral Density in Iranian Children

Background: Bone mass acquisition in childhood is directly linked to adult bone mineral density (BMD) and fracture risk. BMD is a heritable trait, more than 70% of its variability among a population is affected by genetic factors. Objectives: In the present study, we wanted to investigate the association between estrogen receptor alpha (ESR1) polymorphisms, PvuII (rs2234693) and XbaI (rs9340799), and bone area, bone mineral content (BMC), and BMD of the lumbar spine, femoral neck, and also of the total body less the head in Iranian children. Methods: The ESR1 gene PvuII and XbaI genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. Bone area, BMC, BMD, and bone mineral apparent density (BMAD) were assessed by dual-energy X-ray absorptiometry (DEXA). Linear regression was carried out to examine the effects of the ESR1 (PvuII and XbaI) polymorphisms on DEXA outputs when adjusted for confounding factors (i.e., age, sex, BMI, and pubertal stage) in 3 models. Results: ESR1 (PvuII) gene polymorphisms (CT vs. CC) showed significant effects on the BMC of the total body less the head in all 3 models. For ESR1 (XbaI), individuals with the AG genotype had higher lumbar spine BMD and lumbar spine BMAD compared to other genotypes. Conclusions: It seems that the PvuII and XbaI polymorphisms of ESR1 could be associated with BMC and BMD variation in Iranian children and adolescents.

Associations of Estrogen Receptor Alpha Gene Polymorphisms with Type 2 Diabetes Mellitus and Metabolic Syndrome: A Systematic Review and Meta-Analysis.

The associations between PvuII (T>C) and XbaI (A>G) polymorphisms of estrogen receptor alpha (ESR1) gene with type 2 diabetes mellitus (T2DM) or metabolic syndrome (MetS) are reported in many studies, but the results are inconsistent. This present work aims to assess the associations by performing a comprehensive meta-analysis. Relevant studies were searched through several databases. The pooled odd ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the associations of PvuII and XbaI polymorphisms with the risk of T2DM and MetS by using the STATA 14.0 software. Eight studies for T2DM and three articles about MetS were included in this meta-analysis. The overall results indicated that PvuII, rather than XbaI polymorphism, was associated with T2DM (regressive model: OR=0.673, 95% CI=0.550 to 0.823, praw<0.001, pFDR<0.003). The subgroup analysis based on race revealed an association of PvuII polymorphism with the decreased T2DM risk in Chinese population and a relationship between XbaI polymorphism and the reduced T2DM susceptibility in Caucasians. The difference of country may be one source of the heterogeneity for PvuII polymorphism and T2DM. However, neither PvuII nor XbaI polymorphism was related to the risk of MetS. The C allele of PvuII polymorphism presents a protective role in T2DM risk, especially in Chinese people. The G allele of XbaI polymorphism is related to a reduced risk for T2DM in Caucasian population. Nevertheless, neither of PvuII nor XbaI polymorphism is associated with MetS risk.

Estrogen Receptor Alpha (ESR1) Single-Nucleotide Polymorphisms (SNPs) Affect Malignant Melanoma Susceptibility and Disease Course.

The incidence of malignant melanoma in the developed world is continuously increasing. We conducted a case–control study in order to evaluate the association between each of the four estrogen receptor alpha polymorphisms (ESR1 single-nucleotide polymorphisms [SNPs] +2464C/T, −4576A/C, +1619A/G, and +6362C/T) and malignant melanoma susceptibility and disease course. The study population consisted of 205 Caucasian patients who were diagnosed as having malignant melanoma and 208 healthy Caucasian controls. Through DNA genotyping, we identified a SNP-dependent malignant melanoma susceptibility as well as a SNP-dependent effect on the course of disease and response to therapy.

Correlations between Polymorphisms of Estrogen 1, Vitamin D Receptors and Hormonal Profile in Infertile Men

Estrogen receptor alpha (ESR1) polymorphisms (XbaI and PvuII) and vitamin D receptor (VDR) polymorphisms (FokI, BsmI, ApaI and TaqI) are the most frequently studied regarding the correlations with the infertility in males, but the results are controversial.The purpose of this study is to evaluate possible correlations between hormonal markers, VDR and ESR1 genotypes and semen analysis, in order to bring new data for a better understanding of male infertility. 42 infertile men and 28 controls were enrolled. The polymorphisms of VDR gene (ApaI, TaqI, BsmI and FokI) and ESR1 (XbaI and PvuII) were performed by PCR-RFLP, along with hormonal markers. An important correlation between PvuII polymorphism and infertility status was revealed. A significant difference between control and infertility group regarding the presence of BsmI (A>G) and ApaI (G>T) polymorphisms was observed in infertile group, prolactin and DHEA were found to correlate significantly statistic with BsmI GG genotype, whereas ApaI AA genotype correlates with prolactin and SHBG levels. By a multivariate analysis, we demonstrated a cumulative effect of some genetic variants in the hormonal status of infertile patients. Therefore, we show that specific genetic variants of ESR1 and VDR genes may jointly influence human spermatogenesis.

Association between Estrogen Receptor Alpha Gene Polymorphisms and Susceptibility to Idiopathic Scoliosis in Bulgarian Patients: A Case-Control Study.

BACKGROUND:The current consensus on idiopathic scoliosis maintains that it has a multifactorial etiology with genetic predisposing factors.AIM:Estrogen receptor alpha gene has been considered as candidate gene of idiopathic scoliosis.MATERIAL AND METHODS:We conducted a case-control study of Bulgarian population samples (eighty patients with idiopathic scoliosis and one hundred-sixty healthy unrelated gender-matched controls) trying to investigate the association between common genetic polymorphisms of estrogen receptor alpha and the susceptibility to idiopathic scoliosis. Molecular detection of the restriction polymorphisms XbaI and PvuII was performed by polymerase chain reaction following by restriction fragment length polymorphism. The statistical analysis was performed by Pearson’s chi-squared test.RESULTS:Our case-control study showed statistically significant association between the PvuII polymorphism and susceptibility to idiopathic scoliosis and curve progression. No genotype or allele of XbaI polymorphism was found to be correlated with the onset or severity of the disease.CONCLUSIONS:The identification of molecular markers with diagnostic and prognostic value could be useful for early detection of children at risk for the development of scoliosis and for prognosis of the risk for a rapid deformity progression. That would facilitate the therapy decisions and early stage treatment of the patient with the least invasive procedures.

Estrogen receptor alpha polymorphisms and the risk of prostate cancer development.

The main purpose of the study was to evaluate the effect of two polymorphisms in the estrogen receptor alpha, rs2077647 and rs3798577, on the development of prostate cancer, their correlation with selected clinical characteristics, as well as consideration of potential interactions between four estrogen receptor alpha polymorphisms (rs2077647, rs3798577, PvuII, XbaI). The study was performed using 395 patients with histologically verified prostate cancer and 253 healthy male controls. The CC genotype of rs2077647 was significantly associated with prostate cancer (OR=1.61). No association was found between rs3798577 polymorphism and prostate cancer. After stratification of patients according to the age at diagnosis and Gleason score, we observed significant correlation between rs2077647 polymorphism and prostate cancer risk in patients diagnosed before the age of 60 as well as patients with Gleason score<7, while rs3798577 was significantly associated with prostate cancer risk development in patients older than 60 and with Gleason score≥7. Double analysis of each combination of four studied polymorphisms showed that presence of at least three variant alleles was associated with prostate cancer risk in all combinations, while each containing rs3798577 was significantly associated with development of high-grade carcinomas. The present study suggests that rs2077647 polymorphism may be a risk factor for prostate cancer especially in patients diagnosed before the age of 60, while rs3798577 polymorphism could probably serve rather as promoting factor in combination with other polymorphisms in estrogen receptor alpha contributing preferably to development of high-grade carcinomas.

Associations of Estrogen Receptor Alpha and Beta Gene Polymorphisms with Lipid Levels and Insulin Resistance in Men

ObjectiveThe association of four single nucleotide polymorphisms in estrogen receptor alpha (ESR1) and beta (ESR2) genes with lipid levels and insulin resistance in men. Design and methodsLipids, glucose, insulin and HOMA-IR were determined, in a population-based, cross-sectional, cohort of 170 apparently healthy middle-aged Greek men, along with body mass index (BMI), waist circumference (WC) and percentage of body fat content (%fat). Genotyping of ESR1 for PvuII and XbaI and ESR2 for RsaI and AluI polymorphisms was performed. ResultsAssociations of AluI with LDL-Chol (mean±SD, aa 4.3±1.1 vs. Aa 3.7±1.0 and ΑΑ 4.2±1.1, p=0.023) and RsaI with HOMA-IR [median (IQR), RR 1.55 (0.88–2.49) vs. Rr/rr 1.69 (0.72–2.29), p=0.032] were found. Synergistic effects of RsaI and AluI of ESR2 gene on LDL-Chol levels, %fat and WC, as well as a synergistic effect of both ESR1 and ESR2 genes on levels of TChol (p=0.01) and LDL-Chol (p=0.027) were also shown. These findings remained significant after adjustment for potential confounders.Significant independent associations of PvuII with %fat (mean±SD, pp 24.6±5.3 vs Pp 22.4±5.2 and PP 21.2±6.7, p=0.044), and RsaI with %fat (RR 22.6±5.5 vs. Rr/rr 25.2±6.3, p=0.015) and WC (mean±SD, RR 97.4±10.4 vs. Rr/rr 102.6±12.6, p=0.013) were found.Synergistic effects on %fat, between the ESR1 polymorphisms (p=0.004), between the ESR2 polymorphisms and among all four ESR polymorphisms studied were also present. ConclusionsESR2 is associated with LDL-Chol levels and HOMA-IR in men independently of confounders. Body fat is affected by both genes. Furthermore, a synergistic effect of ESR1 and ESR2 on TChol, LDL-Chol and %fat, was shown.

Estrogen receptor alpha polymorphisms, estradiol level, and occurrence of atherosclerosis risk factors in healthy postmenopausal women.

BackgroundThe objective of the study was to analyze the relationship between interaction of polymorphisms in the estrogen receptor alpha gene (Erα) and estradiol (E2), and the occurrence of selected atherosclerosis risk factors in postmenopausal women without the diagnosis of a cardiovascular disease.Material/MethodsThe study covered 210 women, a minimum of 2 years after menopause, with FSH >30 mlU/ml, aged 50–60 years, with no chronic diseases diagnosed. In the women examined, the levels of estradiol, total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides were determined, as well as height, waist circumference (W), hip circumference (R), and arterial hypertension. The BMI and W/H ratio were calculated.Genotyping of the ER-α polymorphism was performed using a polymerase chain reaction and restriction enzymes (PCR-RFLP). The alleles of the XbaI polymorphism were defined as A and G: heterozygote AG, wild type GG and homozygote AA. The alleles of PvuII polymorphism were defined as T and C: heterozygote TC, homozygote TT, and wild type CC.ResultsThe concentration of endogenous estradiol and ERα XbaI and PuvII polymorphisms as independent parameters did not significantly affect the BMI, waist circumference, W/H ratio, levels of CHOL, HDL, LDL, TG, or LDL/HDL, nor the systole and diastole in the postmenopausal women in the study.ConclusionsThe presented study suggests that ERα XbaI AA polymorphism may intensify the beneficial effect of estradiol on the distribution of fatty tissue after menopause; ERα XbaI GG and PuvII TC genotypes may intensify the beneficial effect of estradiol on HDL level; ERα PuvII TT genotype unfavorably modifies the relation between concentration of estradiol and systolic pressure after menopause.

Estrogen receptor-alpha polymorphism in patients with and without degenerative disease of the temporomandibular joint

Aims:The genetic aspect of degenerative joint disease (DJD) of the temporomandibular joint is poorly understood. The prevalence of the estrogen receptor alpha (ER-alpha) gene polymorphism in patients with and without DJD using xbal and pvull restriction fragment length polymorphisms (RFLPs) was studied.Methodology:DNA samples from 42 DJD+ and 36 DJD− subjects were amplified. A 346-base pair long ER-alpha gene fragment containing the two sites of polymorphism in intron 1 was analyzed for xbal and pvull RFLP. Statistical analysis was carried out using Fisher’s exact test and two-group t-test.Results:Five different ER-alpha genotypes were found in both groups. These were PXPX, pxpx, pxPX, PxPX, and pxPx.Discussion:There was a higher number of pxpx and pxPX genotypes in the DJD+ samples compared to the DJD− group, which suggests the presence of polymorphism possibly modulates the ER-alpha activity in bone and contributes to the degenerative process in the joint.

Endothelial function and insulin resistance in early postmenopausal women with cardiovascular risk factors: importance of ESR1 and NOS3 polymorphisms.

Cardiovascular benefits from estradiol activation of nitric oxide endothelial production may depend on vascular wall and on estrogen receptor alpha (ESR1) and nitric oxide synthase (NOS3) polymorphisms. We have evaluated the microcirculation in vivo through nailfold videocapillaroscopy, before and after acute nasal estradiol administration at baseline and after increased sheer stress (postocclusive reactive hyperemia response) in 100 postmenopausal women, being 70 controls (healthy) and 30 simultaneously hypertensive and diabetic (HD), correlating their responses to PvuII and XbaI ESR1 polymorphisms and to VNTR, T-786C and G894T NOS3 variants. In HD women, C variant allele of ESR1 Pvull was associated to higher vasodilatation after estradiol (1.72 vs 1.64 mm/s, p = 0.01 compared to TT homozygotes) while G894T and T-786C NOS3 polymorphisms were connected to lower increment after shear stress (15% among wild type and 10% among variant alleles, p = 0.02 and 0.04). The G variant allele of ESR1 XbaI polymorphism was associated to higher HOMA-IR (3.54 vs. 1.64, p = 0.01) in HD and higher glucose levels in healthy women (91.8 vs. 87.1 mg/dl, p = 0.01), in which increased waist and HOMA-IR were also related to the G allele in NOS3 G894T (waist 93.5 vs 88.2 cm, p = 0.02; HOMA-IR 2.89 vs 1.48, p = 0.05). ESR1 Pvull, NOS3 G894T and T-786C polymorphism analysis may be considered in HD postmenopausal women for endothelial response prediction following estrogen therapy but were not discriminatory for endothelial response in healthy women. ESR1 XbaI and G894T NOS3 polymorphisms may be useful in accessing insulin resistance and type 2 diabetes risks in all women, even before menopause and occurrence of metabolic disease.

The association between estrogen receptor alpha polymorphisms and the risk of prostate cancer in Slovak population

The aim of our study was to evaluate the effect of two polymorphisms in the estrogen receptor alpha, PvuII and XbaI, on the development of prostate cancer within Slovak population, as well as their correlation with selected clinical characteristics. The study was performed using 311 prostate cancer patients and 256 healthy male controls. Both polymorphisms were significantly associated with higher risk of prostate cancer development. At the same time, the CC genotype of PvuII polymorphism (OR = 1.98; 95% CI 0.94-4.21; p = 0.05) and the AG genotype of XbaI polymorphism (OR = 1.74; 95% CI 1.0-3.02; p = 0.04) significantly contributed to the development of low-grade carcinoma, while the AG and GG genotypes of the XbaI polymorphism contributed mainly to the development of high-grade prostate cancer (OR = 1.83; 95% CI 1.12-3.01; p = 0.01 and OR = 2.13; 95% CI 1.06-4.19; p = 0.03, respectively). Similarly, the AG and GG genotypes of XbaI polymorphism showed significant association with prostate cancer in patients with serum PSA level ≥10 ng/ml. Both polymorphisms were found at the same time to be more frequent in patients diagnosed before the age of 60. We conclude on the basis of these results that PvuII and XbaI polymorphisms of estrogen receptor alpha might be associated with prostate cancer risk within Slovak population. Although this is a pilot study and, as such, more detailed investigations are needed to confirm the role of these polymorphisms in prostate cancer development and progression within said Slovak population, our results might still provide a valuable basis for further research with larger patient groups.

Do estrogen receptor alpha polymorphisms have any impact on the outcome in an ART program?

To investigate two of the most studied estrogen receptor alpha polymorphisms (PvuII and XbaI) in combination, in order to evaluate their impact on an ART program outcome. 203 normally ovulating women who underwent IVF or ICSI treatment were genotyped for PvuII and XbaI polymorphisms in ESR1 intron 1 using Real-Time PCR. The relationship between the presence of polymorphic alleles and the ovulation induction parameters and outcome was examined. Women were grouped according to the number of polymorphic alleles they carried in two groups (0-2 versus 3-4 polymorphic alleles). The presence of 3 or more polymorphic alleles was associated with significantly lower E2 levels on the day of hCG administration and a significantly lower rate of good quality embryos. There is an association between ESR1 polymorphisms and some ART parameters such as the level of E2 on the day of hCG administration and the quality of the embryos. These results underline the importance of ESR1 as a candidate gene for the prediction of ovarian response to IVF/ICSI protocols. Future research work concerning several more genes is necessary for a better evaluation of patients before entering an IVF/ICSI program.

Genetic polymorphisms of estrogen receptor alpha and catechol-O-methyltransferase genes in Turkish patients with familial prostate carcinoma

OBJECTIVES:Estrogen is one of the most crucial hormones participating in the proliferation and carcinogenesis of the prostate glands. Genetic polymorphisms in the estrogen metabolism pathway might be involved in the risk of prostate carcinoma development. We evaluated the association between genetic polymorphisms in estrogen receptor alpha (ESR1) and catechol-O-methyltransferase (COMT) genes and the risk of developing familial prostate carcinoma.MATERIALS AND METHODS:In this study, 34 cases with prostate carcinoma whose first-degree relatives had prostate carcinoma and 30 healthy age-matched male controls were enrolled. The genotypes of ESR1 and COMT genes were analyzed employing polymerase chain reaction-restriction fragment length polymorphism method. 34 cases with prostate carcinoma, whose first degree relatives had prostate carcinoma and 14 age-matched male controls were enrolled to analyze the genotype of these two genes.RESULTS:Among control patients, the ESR1 PvuII genotypes of C/C, C/T and T/T were observed in 37%, 26% and 37%, respectively, whereas the C/C, C/T and T/T genotypes were observed in 18%, 41% and 41% of case patients, respectively. Among controls, the ESR1 PvuII allele frequencies of C and T were equally observed, whereas the C and T allele frequencies were observed in 38% and 62% of patients, respectively. Among ESR1 PvuII genotypes there were not any significant difference in terms of genotype (P = 0.199) and allele (P = 0.181) frequencies. Among controls, the ESR1 XbaI genotypes of G/G, G/A and A/A were observed in 33%, 37% and 33%, respectively, whereas the G/G, G/A and A/A genotypes were observed in 12%, 47% and 41% of patients, respectively. Among controls, the ESR1 XbaI allele frequencies of A and G were observed equally, respectively, whereas the A and G frequencies were observed in 65% and 35% of patients, respectively. Among ESR1 Χ baI, there was not any significant difference in terms of genotype (P = 0.111) and allele (P = 0.093) frequencies. But the C/C genotype of the PvuII site and G/G genotype of the XbaI site in the ESR1 gene were associated significantly with the risk of developing prostate carcinoma. The G/G, G/A and A/A genotypes of the COMT gene were observed in 50%, 29% and 21% of control patients and in 53%, 21% and 26% of case patients, respectively. The A and G allele frequencies of the COMT gene were observed in 36.7%, 63.3% of control patients and in 36.8%, 63.2% of case patients, respectively. In COMT gene, there was not any significant difference in terms of genotype (P = 0.843) and allele (P = 0.991) frequencies. But the G/A genotype of the COMT gene had a weak tendency toward increased risk.CONCLUSION:Polymorphisms of ESR1 gene in the estrogen metabolism pathway were associated significantly with familial prostate carcinoma risk. Single nucleotide polymorphisms of low-penetrance genes are targets for understanding the genetic susceptibility of familial prostate carcinoma.