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 ...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.展开更多
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 Pvu...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.展开更多
Twenty-five years ago,Nembrot and colleagues reported amplification of the estrogen receptor alpha gene(ESR1) in breast cancer,initiating a broad and still ongoing scientific debate on the prevalence and clinical sign...Twenty-five years ago,Nembrot and colleagues reported amplification of the estrogen receptor alpha gene(ESR1) in breast cancer,initiating a broad and still ongoing scientific debate on the prevalence and clinical significance of this genetic aberration,which affects one of the most important genes in breast cancer.Since then,a multitude of studies on this topic has been published,covering a wide range of divergent results and arguments.The reported prevalence of this alteration in breast cancer ranges from 0% to 75%,suggesting that ESR1 copy number analysis is hampered by technical and interpreter issues.To date,two major issues related to ESR1 amplification remain to be conclusively addressed:(1) The extent to which abundant amounts of messenger RNA can mimic amplification in standard fluorescence in situ hybridization assays in the analysis of strongly expressed genes like ESR1,and(2) the clinical relevance of ESR1 amplification:Such relevance is strongly disputed,with data showing predictive value for response as well as for resistance of the cancer to anti-estrogen therapies,or for subsequent development of cancers in the case of precursor lesions that display amplification of ESR1.This review provides a comprehensive summary of the various views on ESR1 amplification,and highlights explanations for the contradictions and conflicting data that could inform future ESR1 research.展开更多
目的探讨雌激素受体α(ER-α)基因XbaⅠ、PvuⅡ位点多态性与女性膝骨关节炎(KOA)易感性的关系。方法通过计算机检索Pubmed、EMBASE、CENTRAL、Web of science、Ovid、知网、维普和万方数据库,收集有关ER-α基因XbaⅠ (A/G)或PvuⅡ (T/C...目的探讨雌激素受体α(ER-α)基因XbaⅠ、PvuⅡ位点多态性与女性膝骨关节炎(KOA)易感性的关系。方法通过计算机检索Pubmed、EMBASE、CENTRAL、Web of science、Ovid、知网、维普和万方数据库,收集有关ER-α基因XbaⅠ (A/G)或PvuⅡ (T/C)位点多态性与女性KOA易感性的研究。提取相关数据,计算OR值及95%CI,利用STATA 11软件行Meta分析。结果共纳入7篇文献,9个病例-对照或队列研究,试验组2 194例,对照组2 959例。总体结果显示,XbaⅠ、PvuⅡ位点多态性与女性KOA易感性均无显著相关(P>0.05)。亚组分析结果显示,XbaⅠ位点多态性(G vs A; GG vs AA; GG+AG vs AA; GG vs AG+AA)可显著降低亚洲女性KOA的发病风险(P<0.01);PvuⅡ位点多态性(C vs T; CC vs TT; CC vs CT+TT)可显著增加亚洲女性KOA的发病风险(P<0.01)。结论本研究提示ER-α基因XbaⅠ、PvuⅡ位点多态性与女性KOA易感性存在种族差异,但本实验纳入样本量较少,结论仍需更多研究予以证实。展开更多
目的探讨雌激素相关受体α(estrogen-related receptor alpha,ERRα)对脂多糖(lipopolysaccharide,LPS)诱导大鼠肺微血管内皮细胞(pulmonary microvascular endothelial cells,PMVECs)炎症反应的影响及其机制。方法体外培养PMVECs细胞株...目的探讨雌激素相关受体α(estrogen-related receptor alpha,ERRα)对脂多糖(lipopolysaccharide,LPS)诱导大鼠肺微血管内皮细胞(pulmonary microvascular endothelial cells,PMVECs)炎症反应的影响及其机制。方法体外培养PMVECs细胞株,当细胞处于对数生长期时利用慢病毒转染细胞,并构建稳定低表达的ERRα细胞株。将细胞分别为四组:正常对照组(Ctr组)、正常细胞+LPS处理组(Ctr+LPS组)、shERRα1基因敲低组(shERRα1组)和shERRα1基因敲低组+LPS处理组(shERRα1+LPS组)。予20μg/mL的LPS分别刺激对照组和基因敲低组细胞6、12和24 h后,应用cell counting kit-8(cck-8)检测各组细胞的增殖能力;应用酶联免疫吸附试验(ELISA)检测细胞培养液中的肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)的浓度,于LPS刺激12 h后采用Western blot检测各组细胞ERRα及NF-κB通路的相关蛋白(p-p65、p65、P-IKBα、IKBα)的表达水平。两组变量比较采用SNK-q检验,多组变量比较采用单因素方差分析,方差不齐时则用秩转换的非参数检验。以P<0.05为差异有统计学意义。结果与对照组相比,shERRα1组ERRα蛋白的表达量明显降低(0.09±0.01 vs 0.15±0.01);于LPS刺激6、12和24 h后,与对照组相比,shERRα1+LPS组细胞增殖能力明显降低[(99.68±4.53)%vs(48.62±1.60)%];细胞培养上清液中的TNF-α(ng/mL)、IL-1β(ng/mL)的浓度明显升高,于刺激12 h后变化最为明显(15.76±3.38 vs 5498.91±367.95;14.41±3.86 vs 6014.92±277.33)。同时,shERRα1+LPS组p-p65(0.30±0.5 vs 1.05±0.07)、p-IKBα(0.27±0.04 vs 0.77±0.06)表达量明显升高,而IKBα的表达量明显降低(0.96±0.07 vs 0.14±0.04),差异均具有统计学意义(均P<0.05)。结论ERRα基因通过抑制NF-κB信号通路激活,缓解LPS诱导的大鼠肺微血管内皮细胞炎症反应。展开更多
文摘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.
基金This work was supported by National Natural Science Foundation of China （No. 30973046）.
文摘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.
文摘Twenty-five years ago,Nembrot and colleagues reported amplification of the estrogen receptor alpha gene(ESR1) in breast cancer,initiating a broad and still ongoing scientific debate on the prevalence and clinical significance of this genetic aberration,which affects one of the most important genes in breast cancer.Since then,a multitude of studies on this topic has been published,covering a wide range of divergent results and arguments.The reported prevalence of this alteration in breast cancer ranges from 0% to 75%,suggesting that ESR1 copy number analysis is hampered by technical and interpreter issues.To date,two major issues related to ESR1 amplification remain to be conclusively addressed:(1) The extent to which abundant amounts of messenger RNA can mimic amplification in standard fluorescence in situ hybridization assays in the analysis of strongly expressed genes like ESR1,and(2) the clinical relevance of ESR1 amplification:Such relevance is strongly disputed,with data showing predictive value for response as well as for resistance of the cancer to anti-estrogen therapies,or for subsequent development of cancers in the case of precursor lesions that display amplification of ESR1.This review provides a comprehensive summary of the various views on ESR1 amplification,and highlights explanations for the contradictions and conflicting data that could inform future ESR1 research.
文摘目的探讨雌激素受体α(ER-α)基因XbaⅠ、PvuⅡ位点多态性与女性膝骨关节炎(KOA)易感性的关系。方法通过计算机检索Pubmed、EMBASE、CENTRAL、Web of science、Ovid、知网、维普和万方数据库,收集有关ER-α基因XbaⅠ (A/G)或PvuⅡ (T/C)位点多态性与女性KOA易感性的研究。提取相关数据,计算OR值及95%CI,利用STATA 11软件行Meta分析。结果共纳入7篇文献,9个病例-对照或队列研究,试验组2 194例,对照组2 959例。总体结果显示,XbaⅠ、PvuⅡ位点多态性与女性KOA易感性均无显著相关(P>0.05)。亚组分析结果显示,XbaⅠ位点多态性(G vs A; GG vs AA; GG+AG vs AA; GG vs AG+AA)可显著降低亚洲女性KOA的发病风险(P<0.01);PvuⅡ位点多态性(C vs T; CC vs TT; CC vs CT+TT)可显著增加亚洲女性KOA的发病风险(P<0.01)。结论本研究提示ER-α基因XbaⅠ、PvuⅡ位点多态性与女性KOA易感性存在种族差异,但本实验纳入样本量较少,结论仍需更多研究予以证实。
文摘目的探讨雌激素相关受体α(estrogen-related receptor alpha,ERRα)对脂多糖(lipopolysaccharide,LPS)诱导大鼠肺微血管内皮细胞(pulmonary microvascular endothelial cells,PMVECs)炎症反应的影响及其机制。方法体外培养PMVECs细胞株,当细胞处于对数生长期时利用慢病毒转染细胞,并构建稳定低表达的ERRα细胞株。将细胞分别为四组:正常对照组(Ctr组)、正常细胞+LPS处理组(Ctr+LPS组)、shERRα1基因敲低组(shERRα1组)和shERRα1基因敲低组+LPS处理组(shERRα1+LPS组)。予20μg/mL的LPS分别刺激对照组和基因敲低组细胞6、12和24 h后,应用cell counting kit-8(cck-8)检测各组细胞的增殖能力;应用酶联免疫吸附试验(ELISA)检测细胞培养液中的肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)的浓度,于LPS刺激12 h后采用Western blot检测各组细胞ERRα及NF-κB通路的相关蛋白(p-p65、p65、P-IKBα、IKBα)的表达水平。两组变量比较采用SNK-q检验,多组变量比较采用单因素方差分析,方差不齐时则用秩转换的非参数检验。以P<0.05为差异有统计学意义。结果与对照组相比,shERRα1组ERRα蛋白的表达量明显降低(0.09±0.01 vs 0.15±0.01);于LPS刺激6、12和24 h后,与对照组相比,shERRα1+LPS组细胞增殖能力明显降低[(99.68±4.53)%vs(48.62±1.60)%];细胞培养上清液中的TNF-α(ng/mL)、IL-1β(ng/mL)的浓度明显升高,于刺激12 h后变化最为明显(15.76±3.38 vs 5498.91±367.95;14.41±3.86 vs 6014.92±277.33)。同时,shERRα1+LPS组p-p65(0.30±0.5 vs 1.05±0.07)、p-IKBα(0.27±0.04 vs 0.77±0.06)表达量明显升高,而IKBα的表达量明显降低(0.96±0.07 vs 0.14±0.04),差异均具有统计学意义(均P<0.05)。结论ERRα基因通过抑制NF-κB信号通路激活,缓解LPS诱导的大鼠肺微血管内皮细胞炎症反应。
