Estrogen receptor gene polymorphism in a Chinese population with multiple sclerosis

This study sought to elucidate the role of the Pvull and Xbal polymorphisms of the estrogen receptor gene in 74 Chinese patients with multiple sclerosis, and 95 ethnicity-matched controls, using polymerase chain reaction-restriction fragment-length polymorphism analysis. The results revealed that the P allele of Pvull was significantly more prevalent in multiple sclerosis patients compared with controls （P = 0.019）. While distribution frequencies were significantly increased in female multiple sclerosis patients compared with female controls （P = 0.044）, no significant difference was observed between male patients and controls （P〉 0.05）. Frequencies of Ppxx genotypes were significantly higher in multiple sclerosis patients compared with controls （24.3% vs 12.8%, P = 0.025）. Genotypes and alleles of the estrogen receptor were not associated with age, number of attacks or expanded disability status scale scores of patients with multiple sclerosis. These findings indicate that the Pvull but not the Xbal polymorphism in the estrogen receptor gene is associated with susceptibility to multiple sclerosis in the Chinese population. In addition, women with P allele appear to be particularly susceptible to multiple sclerosis.

Relationship between estrogen receptor gene polymorphism and clinical indexes associated with coronary heart disease

Objective: To investigate the relationship between estrogen receptor(ER) gene and the clinical indexes associated with coronary heart disease (CHD). Methods: By means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), we analyzed ER gene polymorphism in 84 CHD patients and 61 healthy subjects and non-CHD inpatients. The clinical indexes associated with CHD were analyzed in relation to the three ER genotypes. Results: There were significant differences in the incidence of hypertension (58.62%), fibrinogen (Fib) concentration (3.5±0.8 g/L), body mass index (BMI, 25.1±3.2), HDL-C concentration (1.0±0.2 mmol/L) between PP genotype group and other genotype groups (P<0.05). Conclusion: ER gene polymorphism may affect ER-mediated cardiovascular protective effect by modulating the expression of ER.

Estrogen receptor alpha gene polymorphism associated with type 2 diabetes mellitus and the serum lipid concentration in Chinese women in Guangzhou

Background Estrogen might play an important role in type 2 diabetes mellitus pathogenesis. A number of polymorphisms have been reported in the estrogen receptor alpha （ERα） gene （also named ESR1）, including the XbaⅠ and PvuⅡ restriction enzyme polymorphisms of ESR1, which may be involved in disease pathogenesis. The aim of this study was to determine whether ER0t gene polymorphisms are associated with type 2 diabetes mellitus and serum lipid level. Methods Two hundred and ninety-nine patients with type 2 diabetes mellitus were compared with three hundred and forty-one health controls of Guangzhou in China, both were male and postmenopausal female residents at 51--70 years. ESR1 genotyping was performed using polymerase chain reaction （PCR） and PvulI and XbaI restriction fragment length polymorphism （PCR-RFLP） analysis. Results ESR1 allelic frequencies of P, p and X, x alleles were 0.408, 0.592; 0.360, 0.640 in the type 2 diabetes mellitus group and 0.318, 0.682; 0.328, 0.672 in the control group, respectively. In case-control study, there was significant difference in PvuⅡ, but not XbaⅠ, allele frequency between the type 2 diabetes mellitus and control groups （P=0.001 and P=0.122）. When the group was separated into men and women, the difference was significant in women （P〈0.001） but not in men （P=0.854） with the PvulI genotype, and the effect of PvulI variant on the development of type 2 diabetes mellitus was improved with aging. In addition, PvulI genotype was associated with blood glucose [fasting blood glucose （FBG）, postprandial blood glucose （PBG）] and serum lipid [total cholesterol （TC） and low density lipoprotein （LDL）-c] concentration in healthy women. Conclusions PvuII polymorphism of ESRI increases susceptibifity to type 2 diabetes mellitus in Chinese Guangzhou women. ESR1 variants may also impact serum lipid metabolism, which might provide a mechanism connecting ESR1 to type 2 diabetes.

Relationship between bone mineral density and polymorphism ofthe estrogenreceptor genein healthy postmenopausal women in China

Objective To investigate the possible relationship between bone mineral density and polymorphism of the estrogen receptor (ER) gene in Shanghai healthy postmenopausal women Methods 250 unrelated healthy postmenopausal women were selected for bone mineral density (BMD) determination by Dual energy X ray absorptiometry (DEXA) and polymorphism of estrogen receptor gene analyses by polymerase chain reaction restriction fragment length polymorphism (PCR RFLP) Results PvuⅡ polymorphisms of ER gene was associated with low Troch BMD ( P =0 0153) while there was no significant relationship between XbaⅠ polymorphism of ER gene and BMD at any of skeletal sites included in the present study, and the combination of PvuⅡ and XbaⅠ polymorphisms of ER gene was significantly associated with both low Lumbar 2-4 ( P =0 0369) and Troch ( P =0 0384) BMD Multiple stepwise regression analysis also indicated that two combined polymorphisms were correlated significantly with Lumbar 2-4 BMD ( P =0 0254) while this correlation was not revealed at any other skeletal sites Conclusion There is significant relationship between the polymorphism of ER gene and both Lumbar 2-4 BMD and Troch BMD It is significant to explore the pathogenesis of osteoporosis and to prevent the development of osteoprosis by use of molecular

Association of estrogen receptor alpha gene polymorphisms with bone mineral density： a meta-analysis

Background A number of studies have examined the association between estrogen receptor alpha （ESR-a） gene polymorphisms and bone mineral density （BMD）, but previous studies of ESR-a gene Xbal （rs9340799） and Pvull （rs2234693） polymorphisms have been hampered by small sample size, regional restrictions and inconclusive results. Thus a meta-analysis is needed to assess their pooled effects. Methods This study reviewed all published articles indexed in Pubmed using the keywords in the title or abstract. All data were extracted independently by two reviewers using a standard form, the studies were meta-analyzed and minor discrepancies were resolved by authors＇ discussion. Results Twenty seven eligible studies involving 8467 women and 2032 men were identified. The Xbal and Pvull polymorphisms were significantly associated with BMD of the lumbar spine. XX and PP homozygotes had a protective effect in comparison with carriers of the x and p alleles, the effects were more significant in premenopausal women or Western women. At the femoral neck, the results were different. XX served as a protective factor in postmenopausal women, Western women, Western postmenopausal women, and men, while PP was likely to serve as a risk factor in Eastern women, Eastern postmenopausal women, and men. Conclusions The Xbal polymorphism is correlated to BMD at diverse skeletal sites. PP had a protective role for the lumbar spine but might be a risk factor for the femoral neck.

Estrogen receptor gene polymorphisms and bone mineral density in Chinese postmenopausal women

Objective To investigate the relationships between the polymorphisms of estrogen receptor (ER) gene, bone mineral density (BMD) and bone biochemical markers in Chinese postmenopausal women. Methods BMD of lumbar spine and femoral neck were measured using dual-energy X-ray absorptiometry (DEXA)in 186 Chinese postmenopausal women. The PvuⅡ and XbaⅠ polymorphisms of the ER gene were detected using polymerase chain reaction (PCR). Bone biochemical markers, serum alkaline phosphatase, osteocalcin and pyridinoline were measured by ELISA. Results The femoral neck(FN) BMD (Z score) was higher in pp compared to Pp (-0.01±0.12 vs. -0.35±0.09, P<0.05) while lumbar spine BMD (Z score) was higher in XX type compared to Xx and xx genotypes (0.01±0.45 vs -1.53±0.17, -1.29±0.10, P<0.001 and 0.001, respectively). Women without Px haplotype (n=79) had a higher BMD Z-score for the lumbar spine (-1.03±0.14 vs -1.45±0.11, P<0.05) and femoral neck (-0.01±0.11 vs -0.31±0.09, P<0.05) than those who had it (n=107). Conclusions The present study suggested that the pp and XX genotypes of ER gene might play a certain role in maintaining FN and lumbar spine BMD. ER genotypes without Px haplotype might be favorable to bone mass, while those with it might exert some harmful effect on bone mineral density.

Association of Estrogen Receptor Gene Polymorphisms and Primary Biliary Cirrhosis in a Chinese Population： A Case- Control Study

Background： Primary biliary cirrhosis （PBC） is a chronic and slowly progressive cholestatic liver disease characterized by destruction of the interlobular bile ducts and a striking female predominance, The aim of this study was to identity associations between estrogen receptor （ESR） gene polymorphisms with the risk of developing PBC and abnormal serum liver tests in a Chinese population. Methods： Thirty-six patients with PBC （case group） and 35 healthy individuals （control group） from the First Hospital of Jilin University were studied. Whole genomic DNA was extracted from all the participants. Three single-nucleotide polymorphisms （rs2234693~ rs2228480, and rs3798577） from ESR1 and two （rs1256030 and rs1048315） from ESR2 were analyzed by a pyrosequencing method. Demographic data and liver biochemical data were collected. Results： Subjects with the T allele at ESR2 rs1256030 had 1.5 times higher risk of developing PBC than those with the C allele （odds ratio [OR] = 2.1277, 95% confidence interval [CI] = 1.1872-4.5517）. Haplotypes TGC of ESRI rs2234693, rs2228480, and rs3798577 were risk thctors for having PBC. The C allele at ESRI rs2234693 was associated with abnormal alkaline phosphatase （OR 5.2469, 95% CI = 1.3704-20.0895） and gamma-glutamyl transferase （OR = 3.4286, 95% CI = 1.0083-13.6578） levels in PBC patients. Conclusions： ESR2 rs1256030 T allele may be a significant risk factor for the development of PBC. Screening for patients with gene polymorphisms may help to make early diagnoses in patients with PBC.

Estrogen receptor a gene PvulI polymorphism and coronary artery disease： a meta-analysis of 21 studies

The association between the estrogen receptor a gene （ESR1） Pvull polymorphism （c.454-397T〉C） and coronary artery disease （CAD） is controversial. Thus, we conducted a meta-analysis to evaluate the relationship. Data were collected from 21 studies encompassing 9926 CAD patients and 16710 controls. Odds ratios （ORs） with 95% confidence intervals （CIs） were used to assess the relationship between Pvull polymorphism and CAD. The poly- morphism in control populations in all studies followed Hardy-Weinberg equilibrium. We found a significant association between ESR1 Pvull polymorphism and CAD risk in all subjects. When the data were stratified by region, a significant association between ESR1 Pvull polymorphism and CAD risk was observed in Asian populations but not in Western populations. The current study suggests that ESR1 Pvull polymorphism has an important role in CAD susceptibility.

Correlation of estrogen receptor alpha gene polymorphisms and bone mineral density in Chinese women with chronic periodontitis

Background Periodontitis and osteoporosis are one of the frequently encountered diseases in post-menopausal women. Estrogen receptors （ERs） regulated bone metabolism. To investigate the possible effect of ER-elpha （a） gene polymorphisms on bone mineral density （BMD） in pre- and post-menopausal Chinese women with chronic periodontitis （CP）, we provided sufficient quantitative information concerning the correlation between ER gene polymorphisms and BMD in periodontitis. Methods Sixty-five post-menopausal and eighty pre-menopausal CP women, and sixty post-menopausal healthy individuals were recruited in this study. Genomic DNA was extracted from oral mucosa swab sample of each subject by the Chelex-100 method. Determination of the ER-a polymorphisms was performed by polymerese chain reaction-restriction fragment length polymorphism （PCR-RFLP） technique with Xbal and Pvull enzyme. The index for periodontal examination includes clinical attachment loss （CAL） and probing pocket depth （PPD）. BMD was measured by dual-energy X-ray absorptiometry （DEXA）. Results There were no significant differences between the ER-α genotypes of Pvull and Xbal and BMD in post-menopausal and pre-menopausal CP patients, respectively （P 〉0.05）. However, there was association between pre- and post-menopausal CP patients at BMD of lumbar spine L2-L4 （P=0.027） and Ward＇s BMD （P=0.004）. Furthermore, the post-menopausal CP women who carried Pvull TT genotype presented significantly lower Ward＇s BMD than the pre-menopausal CP women （P=-0.007）, meanwhile, the post-menopausal CP women who carried Xbal AA genotype presented significantly lower spine L2-L4 BMD than the pre-menopausal CP women （P=0.003）. Conclusions ER-α gene polymorphisms may be a susceptible indicator for BMD variation of lumbar spine L2-L4 and Ward in Chinese pre- and post-menopausal women patients with CP.

雌激素受体基因多态性与复发性流产的相关性研究

目的 探讨雌激素受体 (ER)基因多态性与复发性流产的相关性。方法 取实验组与对照组妇女外周血 ,采用聚合酶链式反应 限制性片段长度多态性 (PCR RFLP)方法研究ER基因的XbaⅠ和PvuⅡ酶切多态性 ,通过统计学分析探讨ER基因的多态性分布与复发性流产的关系。结果 ER基因PvuⅡ酶切多态性分布与复发性流产存在显著相关性 (P <0 .0 1) ,而ER基因XbaⅠ酶切多态性分布与复发性流产无显著相关性 (P >0 .1)。结论 ER基因PvuⅡ酶切多态性分布与复发性流产显著相关 (P <0 .0 1)。

雌激素受体基因多态性与女性绝经后骨质疏松症中医辨证分型关系的研究

目的 :研究中国绝经后女性雌激素受体基因多态性与绝经后骨质疏松症中医辨证分型的关系。方法 :对 2 4 6名中国绝经后女性 (年龄 4 4～ 80岁 ,平均 65 8岁 ) ,用分子生物学的方法分析内切酶PvuⅡ、XbaⅠ限制性长度片段多态性 (RFLPs) ,运用双能X线骨吸收法分别测其腰椎 (L1～ 4 )和股骨 (粗隆间、股骨颈、Ward′s区 )骨密度 ,根据中医虚证辨证分型标准 ,将研究对象分为肾阴虚型、肾阳虚型和阴阳俱虚型 ,观察雌激素受体基因多态性与骨密度及中医辨证分型的关系 ,RFLPs用Pp(PvuⅡ )和Xx(XbaⅠ )来表示 ,限制性部分缺失者用大写字母表示 ,存在者用小写字母表示。结果 :PPxx基因型 ( 2 1例 )骨密度Z score明显低于其他基因型 ( 2 2 5例 ) ,腰椎 ( - 0 71± 0 4 6) g/cm2 ,粗隆间 ( - 0 31± 0 58) g/cm2 ,股骨颈 ( - 0 84±0 66) g/cm2 ,Ward′s区 ( - 0 96± 0 85) g/cm2 ,该基因型女性中医辨证属阴阳俱虚型。结论 :雌激素受体基因RFLPs与中医辨证分型有关。

雌激素受体基因多态性在中国汉族人群中的分布特点

目的：了解雌激素受体（ＥＲ）基因多态性在中国正常人群中的分布及其在不同种族中分布的差异。方法：通过ＰＣＲ限制性酶切方法对１７２名正常个体的基因组ＤＮＡ中ＥＲ基因ＲＦＬＰ多态性进行了观察，并结合文献进行了不同种族间的分析比较。结果：中国正常人群中ＥＲ基因型以ｐｐ型，ｘｘ型和ｐｐｘｘ型发生频率最高，这种分布特点在正常男女间差异不显著。与其他种族相比较，ＥＲ基因型在中国正常人群中的分布与日本人群中的分布较为接近，而与瑞典，美国人群中的分布差异显著。结论：ＥＲ基因ＲＦＬＰ基因多态性在不同种族间分布存在着明显的差异。

雌激素受体基因多态性与乙型肝炎肝硬化的相关性研究

目的:探讨雌激素受体基因的PvuⅡ,XbaⅠ多态性与乙型肝炎肝硬化的关系,从基因水平上进一步探讨肝硬化的发病机制。方法:采用聚合酶链反应(PCR)-限制性片段长度多态性(RFLP)方法检测并比较了98例乙型肝炎肝硬化患者,72例慢性乙型肝炎患者,84例健康对照组的雌激素受体基因PvuⅡ和XbaⅠ多态性。结果:乙型肝炎肝硬化患者的雌激素受体基因的PvuⅡ多态性的Pp基因型和P等位基因频率明显高于健康对照组和慢性乙型肝炎组,pp基因型和p等位基因频率明显低于健康对照组和慢性乙型肝炎组,差异有统计学意义(P<0.05),PP+Pp基因型患肝硬化的风险是pp基因型的2.23倍(OR=2.23)。雌激素受体基因的XbaⅠ多态性分布在各组间比较,差异均无统计学意义(P>0.05)。结论:雌激素受体基因Pp基因型和P等位基因可能是肝硬化发病的遗传易感基因,pp基因型和p等位基因可能是肝硬化发病的保护基因。

绝经后女性雌激素受体β基因多态性与骨密度的关系

目的探讨绝经后女性雌激素受体β基因(estrogen receptor β,ESR2)CA重复序列多态性及G1082A多态性与骨密度的关系。方法随机数字表法抽取重庆地区绝经后女性200例,采用基因扫描及DNA测序技术分析ESR2基因CA重复序列多态性,采用多聚酶链反应-限制性片段长度多态性法分析ESR2基因G1082A多态性,使用双能X线骨密度仪测量股骨近端及腰椎骨密度。结果以CA重复序列平均数22次为界,将重复序列基因分为短基因(<22)和长基因(≥22),分别以S和L表示。200名绝经后女性中CA重复序列基因型SS、SL及LL的频率分别为25.0%、46.0%及29.0%;G1082A基因型rr、Rr及RR的频率分别为43.0%、42.0%及15.0%;基因型频率分布均符合Hardy-Weinberg平衡(P>0.05)。在校正年龄、绝经年限、身高、体质量和体质指数后,CA重复序列SS基因型者股骨颈骨密度较SL或LL基因型者高(P<0.01),其余部位(大转子、Wards三角和腰椎)各基因型骨密度无统计学差异(P>0.05);G1082A位点各基因型股骨颈、大转子、Wards三角及腰椎骨密度无统计学差异(P>0.05);这2个ESR2基因的多态性位点非连锁不平衡(P>0.05)。结论绝经女性中,ESR2基因第5内含子的CA重复序列多态性可能对骨密度的遗传调节起作用,而ESR2基因第5外显子的G1082A多态性可能对骨密度无明显影响。

雌激素受体基因多态性与慢性牙周炎相关性研究

目的探讨雌激素受体基因多态性与陕西地区慢性牙周炎易感性的关联。方法收集陕西地区109例慢性牙周炎患者和99例牙周健康对照组的颊黏膜拭子,用Chelex-100方法提取全基因组DNA,用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测雌激素α和β受体基因型分布。结果慢性牙周炎组与正常对照组在ER-α受体XbaⅠ基因型分布上有统计学差异,慢性牙周炎组XX型基因频率明显高于正常对照组,尤其在女性患者中此差异显著,男性患者中未见不同;ER-β受体RsaⅠ和AluⅠ基因型在患者组与对照组中分布未见差异。结论慢性牙周炎易感性与雌激素XbaⅠ基因型分布相关,汉族女性群体中ER-α受体XX基因型可能为慢性牙周炎的易感因子。

雌激素受体α基因多态性与子宫内膜异位症的相关性研究

目的:探讨雌激素受体α(ERα)基因多态性在子宫内膜异位症发生中的作用。方法:采用RFLP-PCR和DNA序列测定方法,研究60例子宫内膜异位症患者和56例正常子宫内膜中ERα基因PvuⅡ和XbaⅠ多态性分布情况。结果:ERα基因PvuⅡ基因型(PP、Pp和pp)和XbaⅠ基因型(XX、Xx和xx)分布在子宫内膜异位症患者和正常对照组之间差异无显著。6种基因型组合分析,2组间的差异无显著,子宫内膜异位症Ⅰ/Ⅱ期患者与Ⅲ/Ⅳ期患者之间,ERα基因PvuⅡ基因型和XbaⅠ基因型的分布差异也无显著。结论:ERα基因多态性和子宫内膜异位症发生之间无明显相关性。

CYP1B1基因多态性与卵巢癌易感性的研究

目的:研究CYP1B1基因外显子2密码子119(G-T)、外显子3密码子432(C-G)多态性与卵巢癌遗传易感性的关系。方法:应用等位基因特异性聚合酶链反应(AS-PCR)法对53例卵巢癌患者和30例对照者进行CYP1B1基因密码子119(G-T)、密码子432(C-G)突变分析,用免疫组化SP法进一步研究雌激素受体(ER)、孕激素受体(PR)的表达,分析其是否受CYP1B1基因多态性的影响。结果:CYP1B1基因密码子432中等位基因C、G在卵巢癌组和对照组分布的差异有统计学意义(P<0.05),其中等位基因G使卵巢癌发病风险增加2.71倍。CYP1B1基因密码子432C/G各基因型分布两组间差异有统计学意义(P<0.01),纯合突变(G/G)基因型、杂合突变(C/G)基因型与野生(C/C)基因型相比,患卵巢癌的危险度分别提高了4.53倍和4.43倍。此外,432G/G、C/G基因型者ER阳性表达率高于432(C/C)基因型,三者间有显著差异(P<0.05)。结论:CYP1B1基因密码子432突变等位基因与卵巢癌的发生有一定关系,突变基因型增加了卵巢癌的发病风险,且与ER的表达相关。

原因不明子宫内膜薄雌激素受体α基因多态性及其表达

旨在探讨原因不明子宫内膜薄雌激素受体α(estrogen receptor alpha,ERα)基因多态性及其与表达的关系。选择120名原因不明子宫内膜薄患者为试验组,120名子宫内膜正常人群作为对照组。应用分子生物学的方法分析ERα基因PvuⅡ,XbaⅠ限制性片段长度多态性。通过逆转录-多聚酶链反应(RT-PCR)和Western印迹法分析ERα表达。结果显示,P基因型频率试验组为47.1%,对照组为30.0%,OR值:2.076。试验组X基因型频率为20.8%,对照组为30.4%,OR值:0.602。Pvu II和Xba I限制性片段长度多态性在两组中均呈多态性分布。试验组ERα的mRNA和蛋白质表达均比对照组降低(P<0.05)。由此得出,ERα基因多态性与原因不明子宫内膜薄有关,P等位基因可能是其危险因素,X等位基因可能是其保护因素。ERα在子宫内膜中原因不明子宫内膜薄中的表达低于子宫内膜厚度正常子宫内膜。

猪品种间ESR基因PCR-RFLP的初步研究

利用聚合酶链反应 (PCR)技术 ,检测了不同猪品种的ESR基因PvuⅡ RFLP。结果表明 :品种间基因频率差异极显著 (P <0 .0 1 )。并试分析了PvuⅡ

雌激素受体基因多态性与子宫内膜异位症、子宫肌腺症的相关性研究

目的探讨雌激素受体基因ERα多态性是否与子宫肌腺症、子宫内膜异位症的发病相关。方法应用聚合酶链反应(PCR)和限制性片断长度多态性分析(RFLP)检测68例子宫肌腺症、56例子宫内膜异位症患者和78例正常健康妇女ERα基因型。结果 ERαPvuⅡ基因频率pp、Pp、PP在子宫肌腺症组和对照组分别为:38.2%vs39.7%4、2.6%vs 48.7%、19.1%vs11.5%;XbaⅠ基因型频率xx、Xx、XX在子宫肌腺症组和对照组分别为61.7%vs 56.4%3、2.4%vs 41.0%5、.4%vs 2.6%,两组比较差异无统计学意义(P>0.05)。PvuⅡ基因型频率pp、Pp、PP在子宫内膜异位症组和对照组分别为:44.6%和39.7%、37.5%和48.7%、17.9%和11.5%;XbaⅠ基因型频率xx、Xx、XX在子宫内膜异位症组和对照组分别为64.2%和56.4%、32.1%和41.0%、3.6%和2.6%,两组比较差异无统计学意义(P>0.05);ERα多态性与宫内膜异位症患者临床分期也无关联。结论雌激素受体基因ERα多态性可能与上海地区子宫肌腺症、子宫内膜异位症的发病无关联。