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(ER-α)基因PvuⅡ和XbaⅠ多态性与子宫内膜异位症(EM)的相关关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测85例EM患者和90例健康对照者ER-α基因PvuⅡ和XbaⅠ多态性。结果:ER-α基因PvuⅡ基因型PP、Pp、pp频率在EM组和对照组分别为15.3%、57.6%、27.1%和10.0%、43.3%、46.7%;等位基因P、p频率在子宫内膜异位症组和对照组分别为44.1%、55.9%和31.7%、68.3%;两组差异均有显著性(P<0.05)。P 等位基因患EM 的风险是p等位基因的 1.704倍(OR=1.704,95%CI:1.101-2.635)。ER-α基因XbaⅠ多态性分布在两组间比较差异无显著性(P　>0.05)。结论:ER-α基因PvuⅡ基因多态性与EM的发病有相关性,P等位基因可能是EM发病的遗传易感基因。     

人类雌激素受体基因多态性与子宫内膜异位症关系的研究

目的研究妇女的血中雌激素受体（estrogen receptor，ER）基因多态性与子宫内膜异位症的关系，从而了解子宫内膜异位症的发病基础和影响因素，做到更好的针对病因的预防、诊断、治疗，进一步改善和提高患者的生活质量。方法选取子宫内膜异位症患者40例，平均年龄37，5岁，最终诊断均经腹腔镜或开腹手术病理证实。选取非妇科疾病患者52例作为对照组，平均年龄39．5岁。用分子生物学方法，分析内切酶PvuⅡ、XbaⅠ限制性片段长度多态性（restriction fragment length polymorphism，RFLP），观察ER基因多态性在实验组与对照组中的基因型分布。RFLP用Pp（PvuⅡ）和Xx（XbaⅠ）来表示。同时以聚合酶链反应扩增，对雌激素受体基因上游高变区二核苷酸（TA）重复序列进行纯化和序列分析，探讨其与子宫内膜异位症发病风险的相关性。结果实验组与对照组的PvuⅡ、XbaⅠ限制性片段长度多态性基因型均呈多态性分布，两组没有差异。而雌激素受体基因上游的TA重复序列实验组以15次重复明显高于对照组，表现为明显差异。结论特定的雌激素受体基因上游的TA重复序列与子宫内膜异位症的发病风险可能相关。     

雌激素受体α基因多态性与妊娠肝内胆汁淤积症相关性研究

目的探讨雌激素受体α（ERα）基因多态性与妊娠肝内胆汁淤积症（ICP）发病的关系.方法应用PCR-限制性片段长度多态性（PCR-RFLP）技术,对100例ICP患者（ICP组）和100例正常孕妇（对照组）ERα基因1号内含子Xba Ⅰ和PvuⅡ酶切多态性进行分析.结果（1）对照组ERα基因的Xba Ⅰ基因型XX、Xx、xx频率分别为6%、33%、61%,ICP组分别为2%、33%、65%,两组比较,差异无统计学意义（P＞0.05）;对照组等位基因X、x频率分别为23%、78%,ICP组分别为19%、82%,两组比较,差异也无统计学意义（P＞0.05）.（2）对照组ERα基因的PvuⅡ基因型PP、Pp、pp频率分别为18%、42%、40%,ICP组分别为12%、53%、35%,两组比较,差异无统计学意义（P＞0.05）;对照组等位基因P、p频率分别为39%、61%,ICP组分别为39%、62%,两组比较,差异也无统计学意义（P＞0.05）.（3）ERα基因的Xba Ⅰ和PvuⅡ组合基因型在两组间分布比较,差异无统计学意义（P＞0.05）.结论ERα基因多态性与ICP发病无关.     

雌激素受体基因多态性与妊娠期肝内胆汁淤积症关系的研究

目的研究雌激素受体α（estrogen receptor α，ERα）基因多态性表达，探讨ER基因多态性与江西籍汉族人群妊娠期肝内胆汁淤积症（intrahepatic cholestasis of pregnancy，ICP）的相关关系。方法应用聚合酶链反应、限制性片段长度多态性分析方法分析ERα基因多态性在ICP人群中的分布规律以及ERα基因型、等位基因与ICP的相关关系。结果（1）ERα基因XbaI位点多态性在ICP组和对照组的之间有统计学意义。（2）ERα基因PvuII位点多态性在ICP组和对照组的比较中无统计学意义。（3）ICP组中，突变杂合子基因型Xx的OR值为3．429（95％CI：1．509-7．791），XX、Xx联合分析OR值为3．143（95％CI：1．431-6．905）ICP组和对照组ERα XbaI等位基因频率比较发现X等位基因的相对危险度是x等位基因的2．071倍。（4）PvuII和XbaI联合基因型分布在ICP组和对照组间有统计学差异，杂合子联合基因型PpXx与野生型ppxx之间的差异在ICP组和对照组中有统计学意义，OR值为3．956（95％CI：1．287-12．157）。结论ERα基因XbaI酶切位点限制性片段长度多态性与江西籍汉族人群ICP的发生之间存在相关性。而PvuII酶切位点限制性片段长度多态性与该病无关。X等位基因是ICP发病的易感基因，Xx基因型为易感基因型，单倍体PpXx可能使ICP发病风险升高。     

雌激素受体基因PvuⅡ和XbaⅠ酶切多态性及其上游TA重复序列多态性与子宫内膜癌关系的研究

目的　研究妇女的雌激素受体 (estrogenreceptor,ER)基因多态性与子宫内膜癌的关系 ,从而了解子宫内膜癌的发病因素及影响预后的因素 ,做到早预防、早诊断、早治疗 ,从而改善预后。方法　选取患者 5 2例 ,平均 5 7 5岁。患者的诊断均经手术病理证实。选取非子宫内膜癌患者 5 2例作为对照组 ,平均 5 9 3岁。所有入选者均未服用过激素类药物。用分子生物学的方法分析内切酶PvuⅡ、XbaⅠ限制性片段长度多态性 (re strictionfragmentlengthpolymorphism ,RFLP) ,观察ER基因多态性在实验组与对照组中的基因型分布。RFLP用Pp(PvuⅡ )和Xx (XbaⅠ )来表示。同时对人雌激素受体基因上游的高变区二核苷酸 (TA)重复序列进行纯化、克隆和序列分析 ,阐明该重复序列的重复多态性在实验组与对照组当中的分布情况及与子宫内膜癌的关系。结果实验组X基因型频率为 6 5 4 % ,对照组为 4 4 2 % ,OR值 :2 38(95 %CI 1 0 8～ 5 2 5 ) ,P =0 0 4 8;P基因型 ,OR值 :1 0 9(95 %CI 0 4 9～ 2 4 3) ,P =0 84。PvuⅡ、XbaⅠ限制性片段长度多态性在两组中均呈多态性分布。另外 ,TA重复序列在两组当中也存在着重复次数多态性。结论　实验人群中依XX >Xx >xx基因型子宫内膜癌发病危险呈递减趋势。TA重复序列分别在实验组及对照     

雌激素受体基因限制性片段长度多态性与子宫内膜异位症

目的 探讨雌激素受体(ER)基因限制性片段长度多态性(RFLP)与子宫内膜异位症发病的关系。方法 经手术证实的Ⅰ-Ⅳ期子宫内膜异位症患者50例为实验组,随机选择年龄相当的正常妇女50例为对照组,分别提取外周血白细胞DNA,经PCR扩增,PvuⅡ限制性内切酶酶切,琼脂糖电泳观察结果。结果PP、Pp及pp 3种基因型在子宫内膜异位症组出现例数为6、22和22例,而在对照组分别为10,23和17例,两组差异无显著性(P>0.05);等位基因P与p出现频率差异也无显著性(P>0.05)。结论 ER基因型和等位基因频率可能与子宫内膜异位症发病及疾病严重程度无关。     

汉、维族子宫内膜异位症与雌激素受体基因多态性的关系

目的:观察雌激素受体(ER)基因多态性在新疆维吾尔族(维族)及汉族妇女中的分布及其与子宫内膜异位症(内异症)的关系。方法:应用PCR-RFLP技术,分别检测107名维吾尔族健康妇女(维族对照组)及65例内异症患者(维族内异症组),105名汉族健康妇女(汉族对照组)及85例内异症患者(汉族内异症组)的ER基因XbaⅠ和PvuⅡ酶切多态性。结果:ER基因型频率分布符合Harey-weinberg平衡定律。XbaI酶切多态性基因型频率,等位基因频率分别在维、汉族内异症组及对照组比较,差异无显著性(P>0.05)。但PvuⅡ酶切多态性基因型频率,等位基因频率在维族内异症组与对照组间比较,差异均有显著性(P<0.05),在汉族内异症组与对照组之间比较,差异无显著性(P>0.05)。维、汉族的内异症组和对照组比较,两内异症组的PvuII多态性和两对照组的XbaI多态性差异均有显著性(P<0.05)。结论:ER XbaⅠ酶切多态性与维、汉族内异症发病均无关,而PvuⅡ酶切多态性与维族内异症发病有关,与汉族无关。维、汉族内异症发病可能存在不同的遗传易感因素,PvuⅡ基因多态性可能是维族妇女子宫内膜异位症发病的危险因素之一。     

北京地区汉族妇女的雌激素受体基因多态性分布

目的 研究雌激素受体(ER)基因多态性在中国北京地区汉族妇女中的分布以及与其他种族的差异。方法 通过聚合酶链式反应-限制性片段长度多态性 (PCR-RFLP) 方法研究ER基因的Xba Ⅰ和Pvu Ⅱ的酶切多态性分布。结果 中国北京地区汉族妇女的ER基因型Xba Ⅰ和Pvu Ⅱ的酶切多态性分布为ppxx:7(4.8％),PPXx:10(6.8％),PPxx:3(2.1％),PpXX:2(1.4％),PpXx:51(34.9％),Ppxx:36(24.7％),ppXX:1(0.7％),ppXx:9(6.2％),ppxx:27(18.5％)。结论 检测到中国北京地区汉族妇女ER基因Xba Ⅰ和Pvu Ⅱ相结合的所有9种多态性分布,以Pp Xx以及Ppxx型最为常见。     

北京地区汉族绝经后妇女雌激素受体基因多态性与尺桡骨骨密度相关性研究

目的　研究雌激素受体（ER）基因多态性在北京地区汉族绝经后妇女中的分布及其与骨密度的相关性。方法　对绝经1～4年、年龄49～55岁未行激素替代治疗且无对骨密度有影响疾病的健康绝经后北京市区汉族妇女99例,采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法测定ER基因的XbaⅠ和PvuⅡ酶切多态性,用双能X线吸收测量法检测桡骨骨密度（以骨密度T-score值表示）,方差法分析ER基因多态性与骨密度的关系。结果　ER基因PvuⅡ酶切多态性与尺桡骨松质骨（尺桡骨远端）、密质骨（尺桡骨近端）的骨密度无相关性(P>0.05),而ER基因XbaⅠ酶切多态性与尺、桡骨松质骨、密质骨的骨密度有相关性(P<0.05);XX基因型骨密度值最低密质骨为-1.55±0.37、松质骨为-2.54±0.38,xx基因型骨密度值最高密质骨为-0.95±0.24、松质骨为-1.74±0.16。结论　ER基因XbaⅠ酶切多态性与尺、桡骨松质骨、密质骨的骨密度间显著相关,不同个体的基因差异可能影响骨质疏松症的发生、发展。     

肿瘤坏死因子基因多态性与新疆南部地区维吾尔族妇女子宫颈癌相关性研究

目的:探讨肿瘤坏死因子(TNF)基因多态性与新疆南部维吾尔族妇女子宫颈癌易感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)的方法检测111例维吾尔族子宫颈癌患者和100例健康对照者TNFα基因启动子区308位点及TNFβ基因第一内含子252位点的基因型以及等位基因频率,分析两位点基因多态性与维吾尔族子宫颈癌遗传易感性的关系。结果:子宫颈癌患者TNFα-308 G/A杂合子基因型频率显著高于健康对照组(48.6%vs 18%,P0.01);等位基因A的频率高于健康对照组(61.3%vs 19%,P0.01)。同时发现TNFα-308在新疆维吾尔族子宫颈癌组织中,分化程度越低,G/A基因型所占的比例越高(P0.05),而不同临床分期与TNFα-308基因型的分布差异无显著性;TNFβ-252位点基因型以及等位基因频率与健康对照组相比较差异无显著性(P0.05)。TNFβ-252位点基因多态性与子宫颈癌不同临床分期、分化程度之间差异无显著性(P0.05)。结论:TNFα-308位点基因多态性与维吾尔族子宫颈癌的发生具有相关性,A等位基因可能是维吾尔族子宫颈癌的遗传易感基因,G/A杂合子基因型个体较易患子宫颈癌;TNFβ-252位点多态性与维吾尔族子宫颈癌易感性无关。     

Association of IL-10, IL-18, and IL-33 genetic polymorphisms with recurrent pregnancy loss risk in Iranian women

Recurrent pregnancy loss (RPL) is a heterogeneous disease with three or more consecutive abortions before 20?weeks of pregnancy. Recently, inflammatory factors such as interleukins (IL) have been found to be a significant factor in the RPL. The objective of this study was to investigate the association between RPL and IL-10 (rs1800896), IL-18 (rs1946518) and IL-33 (rs1929992) genes polymorphisms in Iranian women. The study participants consisted of 300 women with RPL and the control group comprised of 300 healthy women with successful delivery. Genomic DNA was extracted from peripheral blood, and genotyping was performed by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). There were no significant differences in the frequencies of genotype and allele in IL-10 gene polymorphism (rs1800896) between patients and control group (p?>?.005). In contrast, there were significant differences in the frequencies of CC genotype in IL‐18 gene polymorphism (rs1946518) between patients and the control groups (p?=?.004; OR =0.990; 95% CI: 0.320–8.855). Also, there were significant differences in the frequencies of GA genotype in IL‐33 gene polymorphism (rs1929992) between patients and the control groups (p?=?.001; OR =0.955; 95% CI: 0.239–9.807). Present study showed that the rs1800896 polymorphism (IL-10) might not play role in RPL in the Iranian population; whereas rs1946518 (IL-18) and rs1929992 (IL-33) polymorphisms may be associated with the risk of RPL in the Iranian women.     

Association between a 45-bp 3'untranslated insertion/deletion polymorphism in exon 8 of UCP2 gene and neural tube defects in a high-risk area of China

Uncoupling protein 2(UCP2) is an attractive candidate gene for screening neural tube defects (NTDs) risk. In this study, polymerase chain reaction and agarose gel electrophoresis were used to determine the distribution of the polymorphism in a case group of 140 deliveries with NTDs, and a control group of 251 normal newborns. We found that the frequencies of allele I and genotypes ID + II were higher in the case group than in the control group (P = .167, OR = 1.4, 95% CI, 0.9-2.1; P = .132, OR = 1.44, 95% CI, 0.89-2.33, respectively); and at low maternal educational level, the frequency of ID + II genotypes was significantly higher in the NTD case group (P < .05, OR = 1.7, 95% CI, 1.01-2.79). The result suggested that the polymorphism in UCP2 may be a potential genetic risk factor for NTDs in a high-risk area of China, and the association was influenced by maternal education.     

Vitamin D receptor polymorphism in the group of postmenopausal women with low bone mineral density

OBJECTIVES: Osteoporosis is a multifactoral disease with aetiology depending from the hormonal, environmental, and genetic factors. One of the suggested candidate gene involved in the pathogenesis is the polymorphic gene encoding for vitamin D receptor (VDR). VDR polymorphism was connected with bone mineral density (BMD) and correlated with onset of osteoporosis. The goal of our study was to determine the role of BsmI polymorphism of VDR gene in the group of postmenopausal women with low bone mineral density. MATERIALS AND METHODS: We have analysed the group of 34 postmenopausal women. The DNA analysis was performed using PCR/RFLP (polymerase chain reaction/restriction fragment length polymorphism) assays. RESULTS: In our investigation we have observed statistically higher frequency of B allele (48.5% vs. 41.2%), the lower frequency of b allele (51.5% vs. 58.8%) and bb genotype (8.8% vs. 42.5%) in the investigated group of postmenopausal women with low BMD. CONCLUSIONS: Our observations could suggest the important role of B allele of the VDR gene in the pathogenesis of osteoporosis in the group of women with low mineral density and possible protective role of b allele in this disease.     

Endothelial nitric oxide synthase polymorphism is not associated with placental abruption in Finnish women

OBJECTIVE: To study whether genetic variability in the gene encoding endothelial nitric oxide synthase (eNOS) affects individual susceptibility to the development of placental abruption during pregnancy. METHODS: One hundred and sixteen pregnant women with placental abruption and 113 healthy controls were genotyped for Glu298Asp polymorphism in the eNOS gene. Chi-square analysis was used to assess the differences in genotype and allele frequencies between the two groups. RESULTS: A statistically similar allelic distribution of eNOS Glu298Asp polymorphism was observed in the two groups, with the frequency of the variant G allele being 66.8% in the abruption group and 68.1% in the control group (OR 0.94, 95% CI: 0.64-1.39; p = 0.76). The genotype distribution of the eNOS polymorphism was also found to be statistically similar (p = 0.72). CONCLUSIONS: The observed genotype data in subjects from eastern Finland suggest that the Glu298Asp polymorphism of the eNOS gene does not contribute to placental abruption in this population.     

亚甲基四氢叶酸还原酶基因677位多态性、高同型半胱氨酸血症与复发性流产

目的:探讨亚甲基四氢叶酸还原酶基因(MTHFR)多态性(C677T)与高同型半胱氨酸(Hcy)血症以及复发性流产之间的关系。方法:采用前瞻性病例对照研究方法,收集71例复发性自然流产患者为病例组,另征集同期58例有正常妊娠史者为对照组,利用PCR-RFLP方法研究MTHFR基因多态性(C677T);同时应用酶法测定血清同型半胱氨酸水平;并随访病例组的妊娠结局。结果:①MTHFR基因677位点的3种基因型在病例组和对照组分布分别为CC:14.1%vs 43.1%、CT:49.3%vs 25.9%、TT:36.6%vs 31.0%,组间比较有极显著统计学差异(χ2=14.7,df=2,P=0.001);其中CC基因型在病例组显著降低(P=0.000,OR=0.216,95%CI:0.093-0.505);T等位基因分布在病例组显著升高(61.3%vs 38.7%,P=0.006)。②129例研究对象中TT基因型血同型半胱氨酸水平显著升高(P=0.000):TT为19.0±9.5 nmol/L、CC为13.1±6.2 nmol/L、CT为11.7±4.0 nmol/L,病例组和对照组高Hcy水平组间无统计学差异(P>0.05)。③病例组中有38.0%(27/71)为高Hcy血症,叶酸治疗有效。结论:MTHFR基因多态性(C677T)与复发性流产有关;MTHFR基因TT型与高Hcy血症有关;叶酸可用于治疗高Hcy血症且有助于改善下次妊娠结局。     

胰岛素基因多态性与多囊卵巢综合征的相关性研究

目的:研究胰岛素(INS)基因多态性与多囊卵巢综合征(PCOS)发病间的相关性。方法:PCOS(216例)和非PCOS(192例,正常对照组)患者记录月经周期,计算BMI,检测其血清生殖激素,采用PCR法,分析INS基因多态性。结果:①与其他人种相比,中国人INS中T等位基因频率较低(7.3%)。②PCOS患者INS的A/A,A/T,T/T基因型分布(分别为0.894,0.097,0.009)与非PCOS人群的分布(分别为0.859,0.135,0.005)无显著差异。③PCOS组中,基因型A/T患者总睾酮(T)值显著高于其他2种基因型的T值,而初潮年龄、BMI和其他血清生殖激素值在各基因型间无显著差异。正常对照组中,BMI及生殖激素在各基因型间均无显著差异。结论:INS-23/HphⅠ单核苷酸多态性与中国汉族女性PCOS发病无相关性,但A/T等位基因的表达可能会影响雄激素水平。     

多囊卵巢综合征与CYP_(17)基因多态性的关联性研究

目的：探讨多受卵巢综合征（PCOS）及其高雄激素血症与CYP(17)基因多态性的关联性。方法；用多聚酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测56例PCOS患者（实验组）及30例正常妇女（对照组）CYP(17)基因的多态性，该基因翻译起始点-34bp处因存在单一碱基的变异（C取代T）产生A1（无变异）及A2（有变异）两个等位基因，经PCR扩增后，用限制性内切酶（MspA1I）消化后电泳检测和比较。结果：PCOS组A1和A2等位基因频率分别为45．5％和54．5％，与对照组差异无显著性；有高雄激素血症的PCOS组A2等位基因出现频率（33／43）显著高于无高雄激素血症者（6／13）（P＜0．05）。结论：CYP(17)基因多态性不是PCOS的主要致病因素，但其A2等位基因的存在可能会改变该基因的表达，对PCOS高雄激素血症的形成起重要的辅助作用。     

胸腺基质淋巴细胞生成素基因多态性与子痫前期的相关性研究

目的 探讨胸腺基质淋巴细胞生成素（TSLP）位点rs1898671、rs2289278,rs2289276及rs764916基因多态性与妊娠妇女子痫前期发生的相关性。方法 收集2012年11月至2013年6月中国医科大学附属盛京医院分娩的孕妇384例。其中病例组181例,对照组203例,病例组又分为子痫前期轻度组（97例）和子痫前期重度组（84例）。选取TSLP4个位点（rs1898671,rs2289276, rs2289278 and rs764916）,利用基质辅助激光解析电离飞行时间质谱（MALDI-TOF MS）技术分析该基因的4个位点。结果 各临床资料在病例组与对照组比较中差异均有统计学意义（P＜0.05）,子痫前期轻度组与对照组比较中除年龄外其他各临床资料比较,差异均有统计学意义（P＜0.05）,子痫前期重度组与对照组以及子痫前期轻度组比较中各临床资料差异均有统计学意义（P＜0.05）。位点rs1898671等位基因频率在病例组与对照组中差异有统计学意义（P=0.043, OR=2.682, 95% CI 1.020～7.054）。结论 TSLP位点rs1898671基因多态性与子痫前期的发病可能具有相关性。等位基因T为子痫前期的危险性等位基因。     

Intercellular adhesion molecule-1 K469E polymorphism in Korean patients with spontaneous preterm delivery

OBJECTIVES: To investigate the association between intercellular adhesion molecule-1 (ICAM-1) gene K469E polymorphism and spontaneous preterm delivery in a Korean population. METHODS: Genomic DNA was extracted from whole blood from 55 women experiencing preterm labor and 153 multiparous women (control group) with a history of at least 2 term deliveries. DNA samples were analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The spontaneous preterm delivery (SPD) group carried the 469E allele significantly more frequently than those in the control group (odds ratio [OR], 1.62; 95% CI, 1.04-2.53). The EE genotype was significantly associated with increased risk of SPD (OR, 2.84; 95% CI, 1.17-6.89; P = 0.02). Allelic frequencies in women with abnormal C-reactive protein levels (K = 0.48; E = 0.52) were significantly different from frequencies in the controls (K = 0.68; E = 0.32) (P = 0.006). CONCLUSIONS: ICAM-1 gene K469E polymorphism may be a candidate region and useful predictor of susceptibility to SPD in the Korean population.