雌激素受体α基因Pvu Ⅱ和Xba Ⅰ酶切多态性与冠心病相关性

目的 探讨中国人群中雌激素受体(ER)α基因Pvu Ⅱ和Xba Ⅰ酶切多态性与冠心病(CAD)的相关性.方法 将2004年4月至2006年12月在中山大学附属第五医院心内科住院的中国南方汉族CAD患者236例为病例组,117例选自健康体检者或同期在我院住院的非CAD患者为对照组,应用聚合酶链反应-限制片断长度多态性(PCR-RFLP)分析的方法,检测CAD组和对照组的ERα基因型,比较其与相关指标的关系.结果 ERα酶切多态性分析结果显示Pvu Ⅱ存在PP、Pp、pp 3种基因型;Xba Ⅰ酶切也可区分出XX、Xx、xx 3型.Pvu Ⅱ多态性中,CAD组P等位基因型频率也显著高于对照组[42.2%(199/472)比33.8%(79/234),P=0.032],pp基因型的高密度脂蛋白水平显著高于P等位基因携带者,两组之间基因型分布差异具有统计学意义(P=0.041),X等位基因在对照组和CAD组分别为16.5%(78/472)和16.2%(38/234),两组基因型和等位基因频率差异均无统计学意义.结论 中国南方汉族人群中ERαPvu Ⅱ酶切多态性与CAD有关,P等位基因可能是CAD独立遗传危险因素;ERα Xba Ⅰ酶切多态性与CAD未发现相关.     

雌激素受体-α基因Xba Ⅰ、 Pvu Ⅱ和BstU Ⅰ多态性与男性骨量的关系

目的 了解雌激素受体-α（estrogen receptor-α,ER-α）基因多态性与男性骨密度（bone mineral density,BMD）的关系。方法 PCR-限制性片段长度多态性检测上海市388名46－80岁无血缘关系的健康汉族男性ER-α基因XhaⅠ、Pvu Ⅱ和BstUⅠ多态性，双能X线吸收仪检查腰椎1－4（L1-4）和股骨近端股骨颈（femoral neck）、大转子区（trochanter）和Ward＇s三角部位BMD。结果 被研究人群XhaⅠ和Pvu Ⅱ等位基因频率分布符合Hardy-Weinberg定律。未发现ER-α基因第1外显子区存在BstUⅠ多态性，所有对象均是BB基因型。XhaⅠ多态性与各部位BMD值均无相关；Pvu Ⅱ多态性与L1-4和Ward＇s三角部位BMD值均有关联（P＜0.05），Pp基因型在上部位平均BMD值明显高于PP和pp基因型（P＜0.05）。结论 本研究结果提示中国汉族人群缺乏或罕有ER-α基因BstUⅠ多态性；ER-α基因PvuⅡ多态性可能影响老年男性松质骨骨量的丢失。     

雌激素受体基因内切酶位点多态在孕妇中分布及其与骨密度和补钙的关系

目的　研究雌激素受体 (ER)基因内切酶位点多态在孕妇 (南京地区 )人群中的分布及其对补钙的影响。方法　采用聚合酶链反应扩增雌激素受体基因 ,再用内切酶PvuⅡ消化扩增产物 ,然后琼脂糖凝胶电泳 ,紫外灯下观察分析和照相 ,根据带型进行ER基因分型。骨密度测量采用单光子吸收法。结果　孕妇中等位基因P所占的比例为 37 2 % (35 4/ 95 2 ) ,p为 6 2 8% (5 98/ 95 2 ) ;基因型为PP :16 % (76 / 476 ) ,Pp :42 4% (2 0 2 / 476 ) ,pp :41 6 % (198/ 476 ) ,符合遗传平衡定律 (Hardy -Weinberglaw)即 (p +q) 2 =1。各种基因型的个体平均骨密度 (g/cm2 )值分别是 :PP =0 745 ,Pp =0 5 6 7,pp =0 5 96结论　在中国妇女中PP基因型的人骨密度较高 ,而Pp ,pp基因型的人骨密度较低 ,占人群的 84% (PP基因型对Pp ,pp基因型的 χ2 值 =1 5 9,0 2 5 >P >0 1)。所以中国妇女的平均骨密度较低 ,大部分孕妇在孕期需要补钙 ,建议每天摄入 6 0 0mg～ 12 0 0mg。     

骨代谢相关基因多态性与盐酸雷洛昔芬对绝经后骨质疏松妇女骨密度和骨转换指标影响的关系

目的了解骨代谢相关基因多态性与盐酸雷洛昔芬( raloxifene,RLX)对绝经后骨质疏松妇女骨密度(bone mineral density, BMD)和骨转换指标影响的关系.方法为随机、对照和双盲试验,入选47～74岁68例无亲缘关系的绝经后骨质疏松汉族妇女,随机分为RLX组和安慰剂组(各34例),RLX组日服RLX 60 mg,安慰剂组服与RLX外观一致的安慰剂,共1年.在服药前、服药后6月和12月时,检测BMD和骨转换指标包括血清1型胶原羧基末端肽(C-telopeptide, CTX)和骨钙素(osteocalcin, BGP).分析雌激素受体1基因(estrogen receptor 1 gene,ESR1)Xba Ⅰ和PvuⅡ位点、ESR2基因RasⅠ位点、维生素D受体基因(vitamin D receptor, VDR)FokⅠ和CDX2结合位点的多态性. 结果共58例完成整个试验,研究结束时RLX组腰椎2～4(L2～4)、全髋部和大转子BMD增加的百分数,以及血清CTX和BGP水平下降的百分数与安慰剂组比较差异均有统计学意义(P<0.05或P<0.01).治疗后12个月,RLX组VDR FokⅠ FF基因型者(n=8)全髋部和大转子BMD值平均下降各为1.98%±4.86%和2.26%±4.73%,而Ff/ff基因型者(n=21)平均增加各为2.52%±2.75%和2.74%±2.97%(P<0.05);ESR1 PvuⅡ位点PP/Pp基因型者(n=17)全髋部BMD明显增加(2.12%±2.78%),而pp基因型者(n=12)呈下降(-1.34%±3.73%)(P<0.05).但上述5个位点多态性与安慰剂组各指标变化均无相关性. 结论 RLX对绝经后骨质疏松妇女BMD的作用受VDR基因FokⅠ和ESR1基因PvuⅡ多态性的调节.在临床选择该药物时,可根据应用对象的基因型做有益决策之用.     

成都地区重度子痫前期患者雌激素受体α基因PvuⅡ和XbaⅠ多态性的研究

目的 探讨雌激素受体αa(estrogen receptor,ESRa)基因变异是否与重度子痫前期发病有关联.方法 采用聚合酶链反应-限制性片段长度多态性分析法对成都地区131例重度子痫前期患者和223名健康孕妇ESRα基因PvuⅡ和XbaⅠ多态性进行分析.结果 ESRα基因PvuⅡ位点T、C等位基因的频率在重度子痫前期组为0.580、0.420.在正常孕妇组为0.576、0.424;Xba Ⅰ位点A、G等位基因的频率在重度子痫前期组为0.763、0.237,在正常孕妇组为0.807、0.193.上述位点在两组间等位基因的频率差异均无统计学意义(P＞0.05).经调整年龄和体重指数因素后,正常孕妇组PvuⅡ位点T等位基因携带者(TT或TC基因型者)收缩压水平显著高于CC纯合型者[(114.00±1.44)mmHg或(114.33±1.21)mmHg vs(108.62土1.91)mmHg,P＜0.05];未见重度子痫前期组该位点对血压水平存在影响.也未见正常孕妇组和患者组Xba Ⅰ位点与血压水平有关联.结论 ESRa基因PvuⅡ和Xba Ⅰ多态性与成都地区汉族人重度子痫前期的发病无关联,但Pvu Ⅱ多态性与正常妊娠妇女的收缩压水平有关.     

广西壮族及汉族人群雌激素受体-α基因多态性的分析

目的：研究雌激素受体-α基因PvuⅡ和XbaⅠ多态性在广西壮、汉两民族中的分布。方法：采用PCR-RFLP方法检测壮族和汉族PvuⅡ和XbaⅠ多态性，比较其在两民族中的分布频率，并与其他种族的分布进行比较。结果：PvuⅡ等位基因P、p频率在壮族与汉族两个民族正常人群中分别为33．6％、66．4％和31．9％、68．1％；XbaⅠ等位基因X、x频率分别为22．4％、77．6％和24．2％、75．8％，在壮、汉两民族中比较差异均无显著性；与瑞典、韩国种族比较，PvuⅡ基因型分布及等位基因频率均存在显著差异。结论：雌激素受体-α基因PvuⅡ多态性与瑞典、韩国种族间分布有明显的差异。这种差异可能是导致一些疾病在不同种族、不同地区间的发生、转归和预后不同的遗传因素之一。     

与骨关节炎相关性雌激素α受体基因 PvuⅡ、XbaⅠ位点多态性Meta分析

背景：目前有不少探讨雌激素受体α基因多态性与骨关节炎易感性的相关性研究,但结果仍有一定的争议。目的：分析雌激素受体α基因PvuⅡ、XbaⅠ位点多态性与骨关节炎易感性的关系。方法：检索PubMed数据库、web of science数据库、万方数据库、中国知网全文数据库、维普数据库、中国生物医学文献数据库发表的有关雌激素α受体(ERα)基因PvuⅡ、XbaⅠ位点多态性与骨关节炎的病例对照研究文献,OR值及95%CI为效应指标,采用固定或随机效应模型进行合并分析,并进行偏倚评估。应用Revman 5.1软件进行统计学处理。结果与结论：共纳入文献9篇,包括3 228例骨关节炎患者,6 327例健康对照。PvuⅡ位点各等位基因及基因型(C vs. T;CT vs. TT;CC vs. TT;CT+CC vs. TT;CC vs. CT+TT)合并OR值均 < 1;按地区分组提示亚洲合并OR值均 > 1(CT vs. TT除外),欧美合并OR值均 < 1。XbaⅠ位点各等位基因及基因型(G vs. A;GA vs. AA;GG vs. AA;GA+GG vs. AA; GG vs. GA+AA)合并OR值均 < 1;按地区分组提示亚洲合并OR值均 < 1,欧美合并OR值均<1(GG vs. GA+AA除外)。结果说明,雌激素受体α基因PvuⅡ、XbaⅠ位点多态性与骨关节炎遗传易感性无关联。然而,PvuⅡ位点发生等位基因突变时亚洲人群骨关节炎遗传易感风险较欧美稍高,相反,XbaⅠ位点隐性遗传模型发生等位基因突变时欧美人群骨关节炎遗传易感风险较亚洲人群稍高。提示不同种族的遗传背景差异可能影响上述变化。中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

南昌地区汉族绝经前女性雌激素受体α基因PvuII遗传多态性与体质量指数的关系(英文)

背景:肥胖是由多基因决定的复杂性疾病,体质量指数是研究肥胖的常用表型。有研究显示一些候选基因与体质量指数变异相关,然而它们之间的相互关系却仍未阐明。目的:探讨雌激素受体α基因(ER-α)PvuII多态性是否与体质量指数的变异相关联。方法:征集了绝经前女性390例,均来自南昌地区江西省人民医院的体检人员,测量其身高和体质量,计算体质量指数。用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)法对所有被试者的雌激素受体α基因PvuII位点进行基因分型。结果与结论:雌激素受体α基因PP,Pp和pp基因型频率分别为0.133,0.485和0.382。雌激素受体α基因型分布符合哈迪-温伯格平衡(P0.05)。雌激素受体α基因PvuII与体质量指数没有显著的关联性(P=0.338)。证实雌激素受体α基因PvuII多态性对南昌地区绝经前妇女体质量指数没有重要的影响。     

雌激素受体-β基因多态性对广西壮族绝经后妇女碱性磷酸酶和骨密度影响

目的 :了解雌激素受体-β基因多态性对广西壮族妇女绝经后妇女血清碱性磷酸酶和骨密度的影响,为绝经后骨质疏松症(PMOP)早期个性化防治提供理论依据。方法 :对612例广西壮族绝经妇女,用超声骨质密度仪进行检测其右侧足跟骨骨密度。早晨空腹采外周静脉血5 ml,PCR-RFLP检测雌激素受体-β基因多态性,用试剂盒法测定各基因型妇女样本对应的血清碱性磷酸酶。结果 :随着年龄增大,绝经早期雌激素受体-β各基因型的血清碱性磷酸酶水平都是升高和骨密度都是降低,雌激素受体-β各基因型之间碱性磷酸酶和骨密度均无明显差别。而60岁后绝经晚期雌激素受体-βRsaI酶切的r等位基因与同一年龄组其他4个基因组比较,血清碱性磷酸酶水平明显升高,而骨密度明显降低;65岁后绝经晚期雌激素受体-βAluI酶切的aa等位基因与同一年龄组其他4个基因组比较,碱性磷酸酶水平明显降低,而骨密度明显提高。结论 :雌激素受体-βRsaI酶切的r等位基因绝经妇女更易患绝经后骨质疏松症,应提前防治。而雌激素受体-βAlu I酶切的aa等位基因绝经妇女不易患绝经后骨质疏松症。绝经后骨质疏松症防治方面,应该根据雌激素受体不同基因型,采取个体化防治,这样更有针对性,提高防治效果。     

西藏藏族人群骨发育候选基因ERα的多态性

目的:分析西藏藏族人群骨发育相关基因,雌激素受体基因α(ERα)多态性分布及其在不同种族和地区间有无差异.方法:随机抽取世居西藏(拉萨、那曲)地区,父母均为藏族,3代内无族外通婚,彼此间无亲缘关系,经体检证明健康的藏族158例.采用PCR-RFLP及琼脂糖凝胶电泳法检测西藏藏族人群的雌激素受体基因α基因PvuⅡ、XbaⅠ多态性.用基因计数法分别计算基因型频率和等位基因频率.结果:西藏藏族正常人群中的雌激素受体基因以pp、xx基因型和p、x等位基因的分布频率为最高,PP、XX基因型和P、X等位基因最低,且男、女间比较差异无统计学意义.但XX基因型与广东、日本、瑞典地区差异有统计学意义,X等位基因与湖南、日本、瑞典地区差异有统计学意义.结论:雌激素受体基因α在西藏藏族人群的分布可能具有种族及民族差异性,不存在性别差异.     

绝经后妇女甲状旁腺素基因多态性与骨密度：福州地区的调查

背景：有研究证实,绝经后妇女骨密度与甲状旁腺素基因有密切关系,但在不同地区人群中结果存在差异性。 目的：探讨福州地区绝经后妇女甲状旁腺素基因(PTH)BstBⅠ多态性与骨密度的关系。 方法：用双能X射线骨密度仪检测福州地区150例绝经后妇女的腰椎、股骨颈,大转子和Ward’s三角骨密度,应用PCR-RFLP技术检测甲状旁腺素基因BstBⅠ多态性。 结果与结论：①甲状旁腺素基因型分布频率为BB型 68.8%、Bb型24.1%、bb 型7.1%。等位基因频率为B 81%,b 19%,基因型分布符合Hardy-Weinberg定律。②分析其基因型与骨密度的关系：BB、Bb、bb 3种基因型在股骨颈、大转子、Ward’s三角区4个部位骨密度差异均无显著意义(P > 0.05)。甲状旁腺素基因BstBⅠ位点多态性与骨密度间无关联,尚不能作为预测福州地区绝经后妇女发生骨质疏松危险的遗传标志。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

The association between postmenopausal vertebral bone mineral density and estrogen receptor gene alleles in ethnic Japanese living in western Japan.

Bone mass and its mineral content has been shown to be under genetic control. Our purpose in this study was to assess whether estrogen receptor genotypes influence changes in bone mass in post menopausal Japanese women and clarify the regional differences in Japanese women. Pvu II and Xba I restriction enzyme fragment length polymorphism of the estrogen receptor gene and its relationship with vertebral bone mineral density were examined in 300 unrelated post menopausal women, aged 42-69 years, from the Kinki region in Japan. Vertebral bone mineral density was evaluated at the lumbar spine (L2-4) by dual energy X-ray absorptiometry. We found no relationship between any single restriction site polymorphism and the Z-score of bone mineral density. However, the allelic haplotype PPXx was found to be associated with a significantly low bone mineral density (Z-score for the lumbar spine -1.118+/-1.270 vs. PPxx 0.04+/-1.150; p<0.01, vs. ppxx 0.387+/-1.226; p<0.05, respectively). We suggest that ER gene polymorphism is associated with low bone mineral density and that this partly explains the cause of post menopausal bone loss in Japanese women. The contradictory conclusions compared with previous studies in the Japanese population regarding the association of BMD with ER RFLPs demands further investigation.     

骨钙素基因Hind Ⅲ多态性与福州地区汉族绝经后妇女骨密度的相关性

背景：骨质疏松症是一种多基因遗传病,骨钙素受体基因多态性与骨密度关系存在地域和人群的差异。 目的：观察绝经后妇女骨钙素基因型频率分布及其与骨密度的关系,探讨福州地区汉族绝经后妇女骨质疏松症的遗传易感基因。 方法：用聚合酶链式反应限制性片段长度多态性分析201例汉族绝经后妇女骨钙素基因型,用双能X射线吸收法测定腰椎、股骨颈,大转子和Ward’s三角4个部位骨密度值。 结果与结论：福州地区汉族绝经后妇女骨钙素基因型频率分布符合Hardy-Weinberg定律(χ²=2.29,P > 0.05),基因多态性分布依次为HH 5%、hh 46%、Hh 49%,与福州、北京、广州、台湾地区骨钙素基因Hind Ⅲ位点多态性分布频率差异无显著性意义(P  > 0.05)。但是与日本人、白种人差异明显(P  < 0.05)。且HH基因型在大转子骨密度明显高于hh型(P < 0.05),但不同基因型在第2~4腰椎、股骨颈、Ward’s三角区的骨密度差异无显著性意义。提示绝经后妇女骨钙素基因型与大转子骨密度可能存在一定关联。     

Association of polymorphisms of the estrogen receptor alpha gene with bone mineral density of the femoral neck in elderly Japanese women

The estrogen receptor alpha gene is a candidate locus for genetic influence on bone mass. The possible association between two polymorphisms in the first intron of this gene, alone or in combination, and bone mineral density at various sites was examined in participants in the National Institute for Longevity Sciences Longitudinal Study of Aging, a population-based prospective cohort study of aging and age-related diseases. The relationship of the TC ( PvuII) and AG ( XbaI) polymorphisms in the first intron of the estrogen receptor alpha gene to bone mineral density was determined in 2230 subjects (1120 men, 1110 women) and in 2238 subjects (1128 men, 1110 women), respectively, all of whom were community-dwelling individuals aged 40-79 years. Bone mineral density at the radius was measured by peripheral quantitative computed tomography and that for the lumbar spine, right femoral neck, right trochanter, right Ward's triangle, and total body was measured by dual-energy X-ray absorptiometry. Estrogen receptor alpha genotypes were determined with an automated fluorescent allele-specific DNA primer assay system. Analysis of the TC ( PvuII) polymorphism revealed that bone mineral density for the total body, femoral neck, and trochanter was significantly lower in women aged 60 years or over with the CC genotype than in those with the TT genotype, but statistical significance was not achieved after adjustment for age, body mass index, and smoking status. Analysis of the AG ( XbaI) polymorphism revealed that bone mineral density for the femoral neck was significantly lower in women aged 60 years or over with the GG genotype than in those with the AA genotype. After adjustment for age, body mass index, and smoking status, bone mineral density for the femoral neck was significantly lower in women aged 60 years or over with the GG genotype than in those with the AA or AG genotypes. Analysis of combined genotypes in women aged 60 years or over revealed that bone mineral density for the femoral neck was significantly lower in women with the CC/ GG genotype than in those with the TT/ AA or TC/ AA genotypes. After adjustment for age, body mass index, and smoking status, bone mineral density for the femoral neck was significantly lower in women aged 60 years or over with the CC/ GG genotype than in those with other genotypes. No differences in bone mineral density at the various sites were detected among TC ( PvuII), AG ( XbaI), or combined genotypes in women aged under 60 years or in men. These results suggest that the estrogen receptor alpha gene is a susceptibility locus for bone mass, especially for the femoral neck, in elderly Japanese women.     

Association of vitamin D receptor and estrogen receptor gene polymorphisms with bone mass in postmenopausal Korean women

OBJECTIVE: To examine the relationship between vitamin D receptor (VDR) and estrogen receptor (ER) gene polymorphism and bone mineral density (BMD). DESIGN: Polymorphisms at the VDR FokI and ER PvuII and XbaI gene sites, serum bone-specific alkaline phosphatase, urinary N-telopeptide of type I collagen, and BMD at the lumbar spine and proximal femur were analyzed in 229 postmenopausal Korean women. RESULTS: The distribution of ER PvuII and XbaI and VDR FokI restriction fragment length polymorphisms was as follows: pp 39.3%, Pp 46.3%, PP 14.4%, xx 34.1%, Xx 61.1%, XX 4.8%. ff 17.0%, Ff 43.7%, and FF 39.3%, respectively (upper-case letters signify the absence, and lower-case letters signify the presence of the restriction site). After adjusting for potential confounding factors such as age, body mass index, and menopause duration, ER PvuII was independently associated with BMD at the lumbar spine and XbaI polymorphism BMD at the femoral neck. The lumbar spine BMD in the pp genotype was 7.5% lower than in the PP genotype, and the femoral neck BMD was 4.8% lower in the Xx genotype than in the xx genotype. By itself, the VDR FokI polymorphism was not related to BMD, but by combining the FokI genotype (FF) with ER genotypes, such as ppxx and the PpXx, the difference in the BMD at the Ward's triangle became significant. There were no significant differences in the levels of biochemical markers between the genotypes of three polymorphisms. CONCLUSION: ER polymorphisms, singly and in relation to VDR FokI polymorphism, influence bone mass in Korean women.     

护骨素基因T245G多态性与老年人骨密度关系的部位及性别差异

背景：作为骨折发生的重要临床预测因子,骨密度在一定程度上由遗传因素决定。护骨素基因是骨质疏松症发病中的重要候选基因。 目的：探讨护骨素基因T245G多态性与骨密度的相关性。 方法：选取2008-09/2010-04在北京大学人民医院进行常规查体的老年人281名,其中男182名,女99名。应用PCR-RFLP结合DNA测序检测护骨素基因T245G多态性,使用双能X射线骨密度测量仪测定受试者腰椎、髋部标准位置及前臂的骨密度。同时收集受试者的生化指标及临床观察项目。应用ANOVA方法分析护骨素基因T245G多态性与各检测指标的关系。 结果与结论：在老年男性及绝经后女性中,T245G基因T,G等位基因频率分布差异无显著性意义(P > 0.05)。在老年男性中,GG和TG基因型具有较高的腰椎骨密度,而TT基因型的腰椎骨密度较低(P < 0.05),Ward’s三角区及前臂骨密度在各基因型间差异无显著性意义(P > 0.05)。在绝经后女性中,T245G多态性与骨密度无关,说明护骨素基因与老年男性腰椎骨密度有关。     

Estrogen receptor alpha polymorphism as a genetic marker for bone loss, vertebral fractures and susceptibility to estrogen

OBJECTIVE: The purpose of the present study was to investigate the possible roles of PvuII and XbaI polymorphisms of the estrogen receptor alpha (ER(alpha)) in bone mineral density (BMD), vertebral fracture, bone loss rate after menopause and response to hormone replacement therapy (HRT). METHODS: All 286 women were grouped according to the genotypes of PvuII or XbaI polymorphisms of the ER(alpha) gene. We compared the BMD Z-score, incidence of vertebral fracture, changes in Z-score after menopause and response of BMD to HRT among the genotypes. RESULTS: Subjects with the PPxx genotype had significantly (P<0.05) lower Z-scores than did subjects with the other genotypes. A negative correlation was observed between the length of time after menopause and the decrease of the Z-score only in women with the pp genotype, suggesting faster bone loss in this group. In the analysis of the ER(alpha) polymorphism with regard to the effect of HRT on BMD, there appears to be a significantly greater increase of BMD (P<0.01 and 0.05) in women with the pp genotype than in those with the Pp or PP genotype. CONCLUSIONS: PvuII and XbaI polymorphisms of the ER(alpha) gene were associated with BMD in postmenopausal Japanese women. Also, the polymorphisms may be useful genetic markers for predicting vertebral fracture in relatively young postmenopausal women. The PvuII polymorphism may be associated with susceptibility to changes in estrogen level.