XbaI Genotypes Research Articles

Effect of interactions between APOE and ESR1 polymorphisms on cognitive functions in postmenopausal women.

IntroductionDuring menopause the level of estrogens is decreased, which may lead to cognitive impairment or dementia. Some forms of genetic polymorphism were found to be related to cognitive functions, including APOE and ESR1 (PvuII and XbaI) polymorphisms. In the present study we aimed to analyze the impact of interactions between APOE and ESR1 polymorphisms on cognitive functions in the group of postmenopausal women.Material and methodsThe study group consisted of 266 postmenopausal women aged 50–65 years without symptoms of dementia. A computerized battery of the Central Nervous System Vital Signs (CNS VS) test was used to diagnose cognitive functions. APOE and ESR1 polymorphisms were genotyped using multiplex PCR and PCR-RFLP methods, respectively. Statistical analysis was performed using two-way analysis of variance in Statistica software.ResultsThe best memory, visual memory, processing and psychomotor speeds were found in women carrying the C allele of the PvuII polymorphism (TC + CC genotypes) in the presence of the APOE ε2/ε3 genotype, while a lower outcome was noted in women with ε3/ε3, and the lowest if they had the ε4 allele. In the case of women with TT genotype of the PvuII polymorphism, cognitive functioning did not decrease in women with the ε4 allele. A similar effect on cognitive functions was observed for AG + GG genotypes of the XbaI and APOE polymorphisms. Women who simultaneously carried CC PvuII and GG XbaI genotypes had the lowest cognitive functions.ConclusionsInteractions of polymorphic variants of APOE and ESR1 genes influenced cognitive functions in postmenopausal women.

Alpha estrogen receptor polymorphisms and their association with breast density.

In the development of breast cancer (BC), estrogen exposure and the increase in breast density (BD) are two determinant factors for BC risk. To identify the relationship between the XbaI and PvuII polymorphisms in the estrogen receptor (ER-alpha) with BD. Cross-sectional study which included 225 women, aged 40-65 years, without evident cancer data, who underwent routine mammography for early BC diagnosis in a radiology department. Two groups were formed: women with increased and with normal BD. Participants were genotyped for the XbaI and PvuII polymorphisms. 19.1% had normal weight, 37.7% overweight, and 43.2% were obese women. In relation to high-risk patterns, 105 women had increased BD and 120 had normal BD (53.3%). The frequency of women with increased BD was also lower in postmenopausal women. Regarding the type of BD, there was no statistically significant difference between frequencies of PvuII and XbaI genotypes. Logistic regression showed that only age and body mass index (BMI) were associated with BD. PvuII and XbaI ER-alpha genotypes were similar among women with dense and non-dense breasts; differently, other factors were associated with BD (age, BMI and menopausal status). Therefore, emphasis should be placed on clinical practice in the relationship between BMI and BD.

The correlation between Erα gene polymorphism and the distribution pattern of fascia syndrome in women with knee osteoarthritis

Objective To study the correlation between Erα gene polymorphism and the distribution pattern of TCM meridian syndrome in women with knee osteoarthritis. Methods A total of 120 Knee osteoarthritis (KOA) female patients admitted to our hospital between January 2018 and December 2018 were selected as the observation group, and 120 healthy female subjects accepted physical examination at our hospital over the same period were selected as the control group. The Erα gene distribution of estrogen receptor was compared between the two groups to identify the differences between KOA women and healthy women. The TCM syndromes and meridians types of the patients in the observation group were defined to evaluate the degree of KOA. The correlation among KOA status, Erαgenotypes, TCM syndromes and meridians was analyzed. Results The distribution of Erα gene XbaI was significantly different between the observation group and the control group (χ2=35.339, P<0.001). There was a statistical difference in the distribution of XbaI genotypes between mild to moderate and severe patients in the observation group (χ2=29.088, P<0.001). There was a moderate correlation between the Lequesne score and the fascia type in KOA women, and a high correlation between the Lequesne score and the TCM syndrome differentiation type, and a moderate correlation between the Lequesne score and the Erα gene and the XbaI genotype (P<0.05). The Erα gene polymorphisms, meridians and syndrome differentiation were moderately correlated (P<0.05). Conclusions In female patients with knee osteoarthritis, the conditions are more serious in patients with complex type of tendons, deficiency of liver and kidney, phlegm and blood stasis, Erα gene xx genotype, and there is a clear correlation between the TCM type of tendons and ER gene polymorphism. Key words: Osteoarthritis, knee; Female; Estrogen receptor alpha; Genotype; Syndrome differentiation classification; Syndrome type

Association of the ESR1 polymorphism with menopause and MLXIPL genetic variant influence serum uric acid levels in Slovak midlife women.

This study examines associations between the ESR1 (XbaI, PvuII) and the MLXIPL (rs3812316) gene polymorphisms, and uric acid (UA) levels in Slovak midlife women, subdivided according to their menopause status. We assessed a total of 362 women from 38 to 65 years of age. Women were recruited from different localities in the western and middle parts of Slovakia. Participants were interviewed during their medical examination at local health centers. They were investigated with respect to a variety of aspects such as medical, anthropometrical, and lifestyle. Participants provided a blood sample for biochemical analyses and DNA genotyping. The MLXIPL gene (rs3812316 SNP variant) and ESR1 gene (PvuII and XbaI) genotypes were then detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Data were analyzed using general linear models and multiple linear regression analyses to adjust for risk factors elevating the UA level such as fat mass (FM), triglycerides (TGs) and creatinine. A positive association between MLXIPL and UA level was observed in the total sample of women after control for confounding covariates, including FM, TGs, and creatinine (P = 0.027). Women with the CC genotype had higher UA levels than the G-allele carriers (261.5 μmol/L ± 68.3 vs 241.1 μmol/L ± 55.1 P = 0.013). A statistically significant association was noticed between postmenopause status and the ESR1 XbaI genotype and their effect on UA (P = 0.028). The Bonferroni pairwise comparison determined that the G-allele carriers in the postmenopausal period had higher estimated UA marginal mean (269.7 μmol/L) than the AA-allele postmenopausal women (236.5 μmol/L) (P = 0.012). The estimated UA marginal mean showed a significant increasing trend according to the MS in G allele carriers (248.5 μmol/L in pre/peri-menopausal vs 269.7 μmol/L in postmenopausal, P = 0.009). In contrast, a decreasing trend was observed in AA carriers (250.6 μmol/L in pre/perimenopausal women vs 236.5 μmol/L in postmenopausal). However, this trend was not statistically significant (P = 0.288). This cross-sectional study suggests that MLXIPL (rs3812316) polymorphism is associated with higher serum UA levels and that the ESR1 (XbaI) polymorphism is associated with UA levels only in the postmenopausal cohort.

Estrogen receptor 1 gene polymorphisms (PvuII and XbaI) are associated with type 2 diabetes in Palestinian women.

BackgroundType 2 diabetes mellitus (T2DM) is a multifactorial disease where both genetic and environmental factors contribute to its pathogenesis. The PvuII and XbaI polymorphisms of the estrogen receptor 1 (ESR1) gene have been variably associated with T2DM in several populations. This association has not been studied in the Palestinian population. Therefore, the aim of this study was to investigate the association between the PvuII and XbaI variants in the ESR1 and T2DM and its related metabolic traits among Palestinian women.MethodsThis case–control study included 102 T2DM and 112 controls in which PvuII and XbaI variants of the ESR1 gene were genotyped using amplicon based next generation sequencing (NGS).ResultsAllele frequencies of both PvuII and XbaI variants were not significantly different between patients and control subjects (P > 0.05). In logestic regression analysis adjusted for age and BMI, the ESR1 PvuII variant was associated with risk of T2DM in three genotypic models (P < 0.025) but the strongest association was observed under over-dominant model (TT+CC vs. TC) (OR = 2.32, CI [1.18–4.55] adjusted P = 0.013). A similar but non-significant trend was also observed for the ESR1 XbaI variant under the over-dominant model (AA+GG vs. AG) (OR = 2.03, CI [1.05–3.95]; adjusted P = 0.035). The frequencies of the four haplotypes (TA, CG, CA, TG) were not significantly different in the T2DM patients compared with control group (P > 0.025). Among diabetic group, an inverse trend with risk of cardio vascular diseases was shown in carriers of CG haplotype compared to those with TA haplotype (OR = 0.28, CI [0.09–0.90]; adjusted P = 0.035). Further, stratified analyses based on ESR1 PvuII and XbaI genotypes revealed no evidence for association with lipid levels (TC, TG, HDL, LDL).ConclusionsThis is the first Palestinian study to conclude that ESR1 PuvII and XbaI variants may contribute to diabetes susceptibility in Palestinian women. Identification of genetic risk markers can be used in defining high risk subjects and in prevention trials.

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.

Identification of XbaI polymorphism of the estrogen receptor alpha in mexicans at early posmenopause

INTRODUCTIONMenopause is the cessation of menstrual cycle, is diagnosed after at least twelve consecutive months whitout bleeding, it occurs due to the reduced functioning of the ovaries, resulting in lower levels of ovarian hormones primarily estradiol (NAMS, 2012). Estrogen suppression has been correlated with higher incidence of cardiovascular and metabolic diseases observed in this age group.Estrogens exert its actions through their receptors, the most studied isoforms of these receptors are: the alpha (ER‐α), beta (Er‐β) and the a G coupled (GPR30). Due to its action and location, an important role in the preservation of cardiovascular and metabolic health has been attributed to ER‐ α (Raushember y Cols, 2016).Several ER‐α polymorphisms have been described, one of the most interesting due to its association with the etiology of cardiovascular pathologies, is the termed as XbaI (rs9340799A&gt; G). This one, consists in the change of an adenine for a guanine, which modifies the affinity of the receptor for its ligand. The X allele has been linked to increased risk of bone demineralization, dyslipidemia, high body mass index (BMI), and oncologic diseases, such as breast cancer and ovarian tumors (chedrahui y Cols,2014; Lobo y Cols, 2014).The aim of this study was to identify the genotype of XbaI polymorphism in mexican posmenopausal women.MATERIALS AND METHODSA descriptive, observational, prospective, transversal, cohort study was carried out in 87 early posmenopausal women who attend to the climacteric clinic of “Hospital general Ignacio Zaragoza”. Clinical data, hormonal profile, blood pressure, antropometric parameters were evaluated. XbaI polymorphism was identified by restriction fragment length polymorphism (RFPL) method.RESULTSThe mean age was 53.01±5.08 years, the BMI average was 28.77±3.88 m/kg2. The averages of systolic, diastolic, and mean blood pressure were 116±10.44 mmHg, 78.7±9.39mmHg y 91.58±9.1 mmHg, respectively;27 patients had hypertension diagnostic under pharmacological treatment.We found 58.87%, 29.89% and 19.24% for xx, Xx and XX genotypes respectively (Graph 1).The averages of systolic, diastolic, mean blood pressure and BMI according XbaI genotype are showed in table 1, there was no statistical differences between groups.CONCLUSIONThe most common genotype in mexican posmenopausal women was xx.There was no differences in blood pressure and BMI according genotype.All patients had elevated values for BMI, independently of her XbaI genotypesSupport or Funding InformationnoneThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Predictive polymorphisms for breast cancer in postmenopausal Mexican women.

Several factors contribute to the increase in breast cancer (BC) incidence, such as lifetime exposure to estrogen, early menarche and older ages at first birth, menopause, and the increased prevalence of postmenopausal obesity. In fact, there is an association between an increased BC risk and elevated estrogen levels, which may be involved in carcinogenesis via the estrogen receptor alpha (ERα) encoded by the ESR1 gene. Interestingly, there is an antagonistic relationship between ERα and the aryl hydrocarbon receptor (AhR) in BC cells. Herein, we explore the combined effects of the ESR1 (XbaI, PvuII) and AhR polymorphisms on BC development in Mexican women according to their menopausal status. Investigation was performed using a cases and controls design. In a group of 96 cases diagnosed with BC and 111 healthy women, the single-nucleotide polymorphisms ESR1 (XbaI, PvuII) and AhR gene were identified by qPCR. Chi-square test or Fisher's exact test were used. Statistical analyses were conducted using the STATA statistical package (Version 10.1, STATA Corp., College Station, TX, USA). The G/G XbaI genotype was more prevalent in the cases than in the controls (P = 0.008). Moreover, Mexican women carrying the XbaI (wild type [WT]/G or G/G) ESR1 genotype have higher risk (12.26-fold) for developing postmenopausal BC than individuals carrying the WT/WT genotype. The presence of the G/G genotype of XbaI may be considered a susceptibility allele in Mexican women. Due to increased postmenopausal BC risk, the XbaI (WT/G or G/G) alleles may be used as a postmenopausal predictive factor for BC in Mexican women.

An analysis of the polymorphisms of the GLUT1 gene in urothelial cell carcinomas of the bladder and its correlation with p53, Ki67 and GLUT1 expressions.

Frequencies of two glucose transporter 1 (GLUT1) single-nucleotide polymorphisms (SNPs) (XbaI G>T and HaeIII T>C) were studied with urothelial cell carcinomas of the bladder (UCC) and 204 normal persons. And the expression of the p53, Ki67 and GLUT1 was assayed by immunohistochemistry. The frequency of the TT genotype and T allele of the XbaI G>T SNP was decreased in the patients with UCC. The frequency of the CC genotype and C allele of the HaeIII T>C SNP was decreased in the patients with UCC. The GLUT1 XbaI genotype GG was more frequent in higher tumor stage and higher tumor grade patients. In the XbaI G>T SNP, the GG genotype was significantly related to higher Remmele immunoreactive score (IRS) of Ki67 and higher IRS of GLUT1. In conclusion, the TT genotype in XbaI G>T SNP and CC genotype of HaeIII T>C SNP may have protective effect in the carcinogenesis process of UCC. In the XbaI G>T SNP, the GG genotype of was positively related to tumor proliferation, glucose metabolism, tumor grade and stage. Therefore, the variant might become a possible proliferation-related prognostic factor for UCC.

A Study on the Role of Estrogen Receptor Gene Polymorphisms in Female Infertility.

Female infertility is often of unknown etiology and is a significant medical problem. It occurs when implantation does not occur; a fertilized embryo fails to survive after implantation; or when the egg cannot move from the ovary to the uterus. The aim of this study was to analyze the role of estrogen receptor 1 (ESR1) genotypes in female infertility. Blood samples were collected from 114 women with infertility undergoing infertility treatment. Samples were also collected from 115 age-matched control women with at least one live child and with no history of infertility or abortions. Genomic DNA was isolated from the blood samples, and genotyping of the ESR1 gene was performed using polymerase chain reaction-restriction fragment length polymorphism. The study revealed the presence of two single nucleotide polymorphisms (SNPs) in the ESR1 gene, PvuII and XbaI. Individual analyses of these two polymorphisms showed that the XbaI heterozygote was significantly increased in controls compared to cases (odds ratio-0.39, confidence interval-0.21 to 0.74, p-0.005). The combined analysis of the PvuII and XbaI genotypes showed no significant difference between the case and control samples. Analysis of the Pvull and Xba1 polymorphisms of the ESR1 gene, demonstrated that the XbaI heterozygote was significantly increased in controls indicating a protective effect.

Influence of estrogen receptor α polymorphisms on bone density in response to habitual exercise in Japanese postmenopausal women.

Estrogen receptor α (ER α) is one of candidate genes for osteoporosis. This study examined the influence of ER α gene, PvuII, and XbaI genotypes on bone density of calcaneus in response to habitual exercise. ER α polymorphisms were detected using PvuII and XbaI restriction enzymes in 316 Japanese postmenopausal women. The bone density was significantly lower in the women carrying PP, pp, or xx genotype without habitual exercise than in the age-matched women without those genotypes. The women carrying Pp genotype without habitual exercise had normal bone density compared to those without Pp genotype. The women carrying PPxx or ppxx polymorphism without habitual exercise had low bone density compared to those with habitual exercise. Thus, the reduction of bone density was attenuated in the women carrying PPxx or ppxx with habitual exercise. In addition, habitual exercise was highly effective for the bone density in the women carrying xx homozygote. These findings indicate that analyses of XbaI and PvuII polymorphisms of ER α may be useful to predict the effect of exercise on bone density, and habitual exercise attenuates the reduction of bone density in women with some genotypes.

Estrogen Receptor Alpha (Esr) Gene Polymorphism As Risk Factor For Type 2 Diabetes Mellitus (T2dm) In Javenese Menopause Women of Indonesia

Background: The number of menopausal women who suffer from low level estrogen-associated type-2 diabetes has been increasing recently. The role of estrogen in metabolism of glucose depends on estrogen receptor alpha expression that is regulated by estrogen receptor alpha gene (ESR ?). PvuII and XbaI polymorphisms in the ESR ? receptor may decrease the expression of ESR ? protein and receptor activity, thereby increasing the risk of developing type 2 diabetes mellitus in menopausal women. Purpose: to determine the ESR ? polymorphism as a risk factor for type 2 diabetes mellitus (DM) in menopause women of Javanese in Indonesia. Methods: Sixty five menopausal women were recruited for the study consisted of 40 women with T2DM and 25 women as control. PvuII and XbaI polymorphisms were determined by polymerase chain reacton-restriction fragment length polymorphism (PCR-RFLP). The absence of PvuII and XbaI restriction sites were indicated by “P1” and “X1” and presence by “P2” and “X2”, respectively. Chai Square test were used in statistical analyisis to measure Hardy Weinberg Equilibrium (HWE) and the risk of P1/P2 and X1/X2 allele for suffering T2DM. Results: PvuII genotype was distributed as; 22.5% (P1P1), 45% (P1P2), 32.5% (P2P2) while XbaI genotype was distributed as 10 % (X1X1), 62.5% (X1X2) and 27.5% (X2X2) in diabetics respectively. There was no difference in distribution of P1 and P2 between diabetics and non diabetics but difference for X1 and X2 existed between groups. The frequency of P2 allele was 55 % while P1 allele frequency is 45% in diabetics. X2 allele frequency was 58.8% while X1 allele is 41.2%. X2 allele had an impact on the 3.6 times higher risk of getting type 2 diabetes in Javanese menopausal women (OR = 3.662, CI = 1.711 to 7.840). Conclusions: PvuII and XbaI polymorphism was found in Javanese menopause women of Indonesia in patients with type 2 diabetes mellitus. The allele frequency of P2 and X2 are 55% and 58.8% respectively. X2 allele was found as a risk factor for type 2 diabetes mellitus in Javanese menopause women of Indonesia. Bangladesh Journal of Medical Science Vol. 12 No. 02 April’13 Page 171-179 DOI: http://dx.doi.org/10.3329/bjms.v12i2.14946

Genetic polymorphims of estrogen receptor alpha −397 PvuII (T&gt;C) and −351 XbaI (A&gt;G) in a portuguese population: prevalence and relation with breast cancer susceptibility

Estrogen receptor alpha (ERα), that mediates the biologic effects of estrogen in estrogen-sensitive tissues like breast, is genetically polymorphic. To evaluate the association between -397 PvuII (T>C) and -351 XbaI (A>G) restriction fragment length polymorphisms (RFLPs) in intron 1 of ERα gene and susceptibility of breast cancer, we undertook a case-control study in BRCA1 185delAG and 5382insC/BRCA2 6174delT negative Portuguese women. The study population consisted of 107 patients with histological diagnosis of breast cancer and 121 women with no history of breast cancer. Genomic DNA was extracted from blood samples and genotyping analyses were performed by PCR-RFLP. XbaI polymorphism was associated with a significant reduced risk of breast cancer for carriers of the x allele in homozygozity (OR 0.178; 95% CI 0.070-0.456; P<0.001) or heterozigozity (OR 0.223; 95% CI 0.089-0.561; P=0.001). The PvuII polymorphism was associated with a non-significantly reduced risk. The combined analysis of PvuII and XbaI polymorphisms revealed none synergistic effect of the two genotypes, except for simultaneous carriers of pp and xx genotypes, that have a reduced risk of breast cancer (OR 0.226; 95% CI 0.049-1.035; P=0.044). The combination of PvuII and XbaI genotypes into haplotypes showed that carriers of two copies of the px (ppxx) haplotype had a reduced risk of breast cancer (OR 0.405; 95% CI 0.194-0.843; P=0.014), compared with PX (PPXX+PPXx+PpXX+PpXx) haplotypes. PvuII and XbaI polymorphisms were in linkage disequilibrium both in cases (D=0.044, r2=0.049, X2=5.216, P=0.022) and controls (D=0.090, r2=0.139, X2=16.819, P<0.001), but not in the entire sample population analyzed as a whole (D=0.087, r2=0.0076, X2=1.733, P=0.188). In conclusion, in this case-control study we found that ERα gene XbaI polymorphism may modify individual susceptibility for breast cancer in this population.

Influence of the XbaI polymorphism in the estrogen receptor-α gene on human spermatogenic defects

Polymorphisms of estrogen receptor (ER) genes have been implicated in male infertility, but studies of this association have produced conflicting results. The present study was conducted to examine whether polymorphisms within the ERα and ERβ genes are susceptibility factors for human male idiopathic infertility in Chinese men. We investigated the association between the ERα gene gene and PvuII and XbaI polymorphisms and the ERβ gene and RsaI and AluI polymorphisms and idiopathic male infertility in Han Chinese men. A total of 204 men with oligozoospermia (sperm count <20 x 10(6)/mL) or azoospermia and 252 fertile control men were included in this study. The analysis revealed a strong association between the XbaI genotype distribution and impaired spermatogenesis (P = 0.0018). The frequency of the G allele was significantly lower in patients than in controls (P = 0.003). Furthermore, serum levels of follicle-stimulating hormone and luteinizing hormone in XbaI AA carriers were significantly higher than those in AG or GG carriers. Our findings further support a possible role of ERα in male infertility. Further studies are needed to replicate our findings, as well as to elucidate more fully the biological mechanisms of the modulation of ERα on human spermatogenesis.

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.

Association of estrogen receptor alpha (ERα) gene polymorphisms with endometrial thickness and lipid profile in women with breast cancer treated with aromatase inhibitors

Aromatase inhibitors (AIs) provide an alternative to tamoxifen as an adjuvant therapy for post-menopausal, hormone-receptor positive breast cancer patients. The aim of the present study was to evaluate the effect of PvuII and XbaI polymorphisms of the ERα gene at ΑΙs treatment’s adverse effects in post-menopausal women with breast cancer. The study included 87 post-menopausal women with ER-positive breast cancer treated with AIs and 80 healthy controls. The overall presence of ERα polymorphisms in all women with breast cancer was not different from the healthy controls. Endometrial thickness under AIs treatment was reduced from (mean value ± SD) 6,404 ± 2,901 mm to 3,666 ± 1,4656 mm. Moreover, the AA XbaI genotype was associated with greater reduction in endometrial thickness during therapy with AIs (p = 0.005). The presence of the CC PvuII and the AA XbaI genotypes were associated with elevated LDL levels and elevated triglycerides. In conclusion, the results of the present study showed that the genotype of women with breast cancer under AIs treatment might influence treatment’s adverse effects, as, the presence of the CC PvuII and the AA XbaI genotypes of the ERα were associated with elevated LDL and triglycerides serum levels, while the AA XbaI genotype was associated with a greater reduction in endometrial thickness.

Estrogen receptor gene polymorphisms in a group of postmenopausal Turkish women: association with bone mineral density

ABSTRACTObjective To evaluate the frequency of the estrogen receptor (ER) gene PvuII and XbaI polymorphisms and their associations with bone mineral density (BMD) in a group of postmenopausal Turkish women.Design A total of 125 healthy postmenopausal women and 125 premenopausal healthy young women as controls were included in the study. The PvuII and XbaI polymorphisms in the ER gene were studied by the polymerase chain reaction-restriction fragment length polymorphism method. The BMD of the lumbar vertebrae and femoral neck were measured by dual-energy X-ray absorptiometry.Results The frequencies of the ERα PVuII genotypes PP, Pp and pp were 20%, 54.4% and 25.6% in premenopausal and 24.8%, 44.8% and 30.4% in postmenopausal women, respectively. The frequencies of the ER XbaI genotypes XX, Xx, xx were 16.8%, 48.8% and 34.4% in premenopausal and 16.8%, 48% and 35.2% in postmenopausal women, respectively. There was no difference in the frequencies of ER gene polymorphisms between premenopausal and postmenopausal women. BMD measurements were not different between ER PvuII and XbaI genotypes in premenopausal and postmenopausal women.Conclusions ER gene PvuII and XbaI polymorphisms have no major influence on bone mineral density in our group of postmenopausal women.

Association of estrogen receptor α gene PvuII and XbaI polymorphisms with non-small cell lung cancer

Single nucleotide polymorphisms (SNPs) of the estrogen receptor (ER)-α have been found to be associated with various diseases at significantly different frequencies. However, whether any relationship exists between ER-α polymorphisms and lung cancer remains to be determined. In this study, 84 non-smoking, female, non-small cell lung cancer patients with various stages of disease and 234 cancer-free reference controls were enrolled to examine the association of ER-α polymorphisms in lung cancer. Two restriction SNP sites, PvuII and XbaI, in the first intron of the ER-α gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of the PvuII-XbaI haplotypes and genotypes in a Taiwanese population were revealed for the first time. Although the genotypic frequencies of two polymorphic sites of ER- α were in linkage disequilibrium for the lung cancer group (χ(2)=50.013, d.f.=4) and reference controls (χ(2)=60.797, d.f.=4); and 7 and 8 combined genotypes were present, respectively, the distribution and the major genotypes are different in the two groups (p<0.0001). The p-values for PvuII and XbaI genotypes were significantly different between the lung cancer and reference controls. The PP genotype presence was found to be significantly lower in the lung cancer group (P=0.005), whereas presence of the xx genotype was significantly higher (P=0.042). These findings suggested that the PP genotype had a lower risk of lung cancer; whereas the xx genotype had a higher risk. In comparison with other studies conducted in various populations, it is of note that the pX haplotype frequency of this study was higher than that of other studies, whereas the px haplotype was lower. Moreover, the Xx genotypic frequency of XbaI polymorphisms in the ER-α gene of the reference control group was found to be extremely high, whereas the xx genotypic frequency was extremely low. In conclusion, PvuII-XbaI polymorphisms of the ER-α gene were found to be associated with the risk, but not cancer severity, of non-small cell lung cancer in a Taiwanese population.

Estrogen receptor alpha gene polymorphisms are associated with type 2 diabetes and fasting glucose in male subjects

The PvuII and XbaI polymorphisms of the estrogen receptor α (ER1) gene have been variably associated with type 2 diabetes (T2D) in several populations. However, this association has not been studied in Iranian subjects and we hypothesized that the ER1 variants might be associated with T2D and related metabolic traits in this population. The PvuII and XbaI genotypes were determined by PCR-RFLP in 377 normoglycemic controls and 155 T2D patients. Bonferroni correction was applied for the correction of multiple testing. No significant association was found between the allele and genotype frequencies of PvuII and XbaI variants with T2D in females. In a dominant model (PP vs. Pp+pp), the frequency of the Pp+pp genotype was higher in normoglycemic subjects compared to T2D patients [85.5% vs. 66.7%, OR 0.22 (0.08-0.55), P=0.001]. Four possible haplotypes were observed in the population, whereas haplotype TA had a higher frequency in male T2D subjects than the controls. Furthermore, non-diabetic male subjects carrying the genotype of PP had a higher fasting glucose levels than the individuals with the genotype of Pp+pp (P=0.013). Multivariate logistic regression analysis showed that PvuII polymorphism was the independent determinants of T2D in males [OR 4.37 (1.61-11.86), P=0.004]. No association was found between the XbaI polymorphism and diabetes in male group. Our results suggest that the ER1 polymorphisms might associate with T2D and fasting glucose among Iranian male subjects.

Combined effect of menopause age and genotype on occurrence of breast cancer risk in Pakistani population

Cancer incidences and mortality rates are rapidly increasing and breast cancer is among the most frequent malignancy experienced in women worldwide. The occurrence of breast cancer could be associated with various social, cultural, environmental, life-style, hormonal and genetic factors. Objective To establish if PvuII and XbaI polymorphisms of estrogen receptor alpha would make Pakistani women more susceptible to breast cancer. Furthermore, association between breast cancer and various factors was also explored to establish the contributing factors in breast cancer in Pakistani population. Subjects and methods Two hundred samples, aged 15–65 years, consisting of 100 breast cancer patients and 100 control samples were ascertained for this case–control study in order to evaluate the factors related to disease incidence. 5–7 ml of blood sample of each participating women in the study was collected and analyzed for polymorphisms of PvuII and XbaI using PCR-RFLP method. Results The menopause had strong influence on incidences of cancer with ca 18-fold increase in risk of breast cancer in women with menopause compared with non-menopaused. Furthermore significant impact of menopause age ( P < 0.0001) was observed on the incidence of cancer, as high rate of cancer incidence was observed in patients with age between 36 and 45 years ( P < 0.0001). Similarly, the genotype XbaI had significant influence on the incidence of the disease with heterozygous genotype of XbaI was 45% higher than wild type in cancerous cases. The menopausal women having heterozygous and homozygous mutants of PvuII or XbaI genotypes were strongly correlated with breast cancer ( P < 0.01). Conclusion The polymorphism of genes involving estrogen-metabolizing pathway and estrogen receptor pathway may play an important role in the etiology of breast cancer in Pakistani women.