胰岛素降解酶基因多态性与多囊卵巢综合征相关性的研究

目的:探讨胰岛素降解酶基因(IDE)多态性与多囊卵巢综合征(PCOS)发病的关系。方法:用聚合酶链反应-限制性片段多态性技术,检测315例PCOS患者(PCOS组)和327例健康妇女(对照组)的IDE基因多态性。结果:IDE基因rs1887922位点基因型分布及等位基因频率在PCOS组总体以及各亚组(胰岛素抵抗组及非胰岛素抵抗组),与健康对照组之间比较均无显著差异。而IDE基因rs2209972位点基因型分布虽然在P- COS组总体及非胰岛素抵抗亚组与健康对照组之间比较无显著差异;但PCOS组总体相应位点的C等位基因频率高于对照组,差异有显著性(P<0.05),PCOS胰岛素抵抗亚组相应位点的基因型频率及等位基因频率均高于对照组,差异有统计学意义(P<0.05)。rs2209972位点不同基因型PCOS患者空腹胰岛素水平及HOMA-IR存在显著差异(P<0.05)。结论:胰岛素降解酶基因多态性可能与PCOS患者胰岛素抵抗相关。     

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。     

钙蛋白酶10基因SNP-43与多囊卵巢综合征相关性研究

目的:探讨钙蛋白酶10基因(CAPN10)的单核苷酸多态性SNP-43 G/A多态与多囊卵巢综合征(PCOS)患者发病的关系。方法:采用病例对照研究方法,以聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,对在山东省立医院生殖医学中心就诊的107例PCOS患者(PCOS组)和126例正常妇女(对照组)的CAPN10 SNP-43进行基因分型,并测定基础状态下的性激素水平及代谢指标。结果:SNP-43 G等位基因在PCOS组和对照组中的分布频率均为100%,未发现A等位基因,两组间比较差异无显著性(P>0.05)。结论:钙蛋白酶10基因SNP-43 G等位基因与多囊卵巢综合征的遗传易感性无明显相关性。     

抗苗勒管激素及其Ⅱ型受体基因多态性在多囊卵巢综合征患者表达的研究

目的:研究抗苗勒管激素(AMH)及抗苗勒管激素Ⅱ型受体(AMHRⅡ)基因多态性在多囊卵巢综合征( PCOS)患者的表达情况;同时分析PCOS不同AMH基因型患者体重指数(BMI)、性激素水平之间是否存在差异,从基因水平探讨PCOS的发病机制.方法:采用聚合酶链反应(PCR)及DNA正、反向测序方法,检测94例PCOS患者(PCOS组)及94例正常排卵患者(对照组)AMH和AMHRⅡ基因型,同时将两组AMH、AMHRⅡ不同基因型患者的年龄、BMI及性激素水平分别进行比较.结果:①两组AMH基因型分布比较,差异有统计学意义(P＜0.05),而AMH等位基因频率、AMHRⅡ基因型分布及等位基因频率分布比较,差异均无统计学意义(P＞0.05).②在PCOS组不同AMH基因型患者中,BMI、LH、T间差异有统计学意义(P＜0.05),基因型分布类型与BMI、LH、T有关(P＜0.05),而与年龄、FSH、E2、PRL无关(P＞0.05);对照组年龄、BMI、性激素水平与AMH基因型分布无关(P＞0.05).③对照组和PCOS组年龄、BMI、性激素水平与AMHRⅡ基因型分布无关(P＞0.05).结论:AMH基因的多态性可能与PCOS的发病相关;PCOS患者AMH基因型中G/T表型可能是引起患者肥胖、高雄激素血症的原因.     

PAI-1基因4G/5G多态性与PCOS糖代谢、肥胖的相关性研究

目的:探讨纤溶酶原激活物抑制因子-1(PAI-1)基因启动子4G/5G多态性与多囊卵巢综合征(PCOS)糖代谢、肥胖的关系。方法:PCR-RFLP法检测42例正常育龄妇女,101例PCOS患者[根据糖代谢情况分为A、B、C组;根据体重指数(BMI)分为肥胖、非肥胖组]PAI-1基因启动子4G/5G位点插入或缺失多态性,比较组间多态基因型分布及体重指数(BMI)、胰岛素抵抗指数(Homa-IR)、胰岛素敏感指数(ISI)。结果:①BMI、Homa-IR指标PCOS糖代谢C组>B组>A组、肥胖PCOS组>非肥胖PCOS组,ISI则相反,差异均有显著性(P<0.05)。②PCOS组不同糖代谢组PAI-1基因4G/5G多态基因型分布无差异,但PCOS组、PCOS糖代谢异常C组与对照组、PCOS非肥胖组与肥胖组之间比较有统计学差异(χ2=4.439、4.018、4.151;P均<0.05);4G型(4G/4G基因型)PCOS组、PCOS糖代谢异常C组与非肥胖PCOS组分布显著高于相应对照组与肥胖PCOS组;5G型(4G/5G+5G/5G基因型)分布相反。结论:①PCOS患者高PAI-1 4G/4G多态基因型,可能是其高PAI-1活性现象的重要遗传基础。②PAI-1基因启动子4G/5G多态性可能与PCOS患者糖代谢异常、非肥胖PCOS发病、病情进展有关。     

卵泡刺激素受体基因与多囊卵巢综合征关系的初步研究

目的:探讨卵泡刺激素受体基因第7、10(A)外显子基因突变与多囊卵巢综合征(PCOS)发病的关系。 方法:提取56例PCOS患者及38例对照者的外周血基因组DNA,采用PCR及RFLP(限制性片段长度多态性)方法研究FSHR第7、10(A)外显子基因多态性。 结果:PCOS组FSHR第7外显子49/49型96.43%,86/49型3.57%,第10(A)外显子128/128型98.21%,128/216型1.79%,与对照组相比较,其基因型分布差异无显著性(P>0.05)。PCOS组第7外显子49型等位基因频率为98.21%,86型等位基因频率为1.79%,第10(A)外显子128型等位基因频率为99.11%,216型等位基因频率为0.89%。结论:中国人群存在以上两位点突变,但突变率在PCOS组及对照组不存在差异。PCOS组LH /FSH比值、高雄激素血症与等位基因86型、216型存在一定的相关趋势。     

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。     

雄激素受体(CAG)_n基因多态性与多囊卵巢综合征相关性的Meta分析

目的评价雄激素受体(androgen receptor,AR)(CAG)n基因多态性与多囊卵巢综合征(polycystic ovary syndrome,PCOS)易感性的相关性。方法检索Pubmed、Embase、CNKI、VIP、万方数据库,英文检索词为androgen receptor,polycystic ovarian syndrome,中文检索词为雄激素受体和多囊卵巢综合征,收集有关AR(CAG)n基因多态性与PCOS易感性的病例对照研究,进行Meta分析。结果共纳入12篇文献,PCOS组1 697例,对照组(健康女性)1 984例。Meta分析结果显示,PCOS组与对照组间AR(CAG)n重复序列长度比较,差异无统计学意义[标准化均数差(SMD)=-0.05,95%CI:-0.19~0.08,P=0.440]。PCOS患者中,高雄激素血症(hyperandrogenism,HA)患者与非HA患者间AR(CAG)n重复序列长度比较,差异无统计学意义(SMD=0.56,95%CI:-0.13~1.25,P=0.110)。结论 AR(CAG)n基因多态性可能与PCOS及其并发的高雄激素血症的发生无关联。     

Vaspin基因多态性与多囊卵巢综合征的相关性

目的:研究Vaspin基因多态性与多囊卵巢综合征(PCOS)的关系。方法:选择2011年7月—2014年8月天津市中心妇产科医院确诊的PCOS患者200例为PCOS组,对照组选取非PCOS且无糖代谢异常的200例正常体检者。观察2组Vaspin rs2236242位点基因多态性基因频率的差别。结果:2组Vaspin rs2236242位点A等位基因与T等位基因频率比较,差异有统计学意义(OR=0.68,95%CI:0.51~0.91,P=0.009)。共显性遗传模型分析显示,TA基因型(OR=0.51,95%CI:0.33~0.79,P=0.002)和AA基因型者(OR=0.47,95%CI:0.23~0.95,P=0.035)的PCOS发病风险低于TT基因型者。显性遗传模型分析显示,TA+AA基因型者PCOS发病风险低于TT基因型者(OR=0.50,95%CI:0.33~0.77,P=0.001)。隐性遗传模型分析显示,AA基因型与TT+TA基因型者PCOS发病风险相似(OR=0.71,95%CI:0.37~1.38,P=0.317)。结论:Vaspin rs2236242位点基因多态性与PCOS发病有关,等位基因A及AA、TA基因型对PCOS发病可能起抑制作用。     

多囊卵巢综合征患者胰岛素受体基因外显子17的多态性研究

目的　探讨胰岛素受体基因外显子17与多囊卵巢综合征(PCOS)发病的关系。方法对33例PCOS患者(PCOS组)和28例因单纯输卵管原因或男性不育的不孕妇女(对照组)的胰岛素受体基因外显子17进行PCR扩增、单链构型多态性电泳分析,及等位基因分布频率比较。同时对各基因型患者进行内分泌检测。结果　两组胰岛素受体基因外显子17的1008bp处,均有T基因型向C基因型(T→C)的突变,均发现了3种基因型,即T/T、C/T、C/C基因型。PCOS组C/C基因型为39%,对照组为11%,两组比较,差异有统计学意义(P<0 .05 );PCOS组C/C基因型肥胖患者为47%,非肥胖患者为33%,两者比较,差异无统计学意义(P>0 .05)。PCOS组合并胰岛素抵抗患者为50%,无合并胰岛素抵抗患者为36%,两者比较,差异无统计学意义(P>0 .05)。PCOS组患者胰岛素敏感指数,T/T基因型患者为0 .038±0 .016,C/C基因型患者为0 .024±0 .010,C/T基因型患者为0 .028±0 .014,C/T基因型及C/C基因型与T/T基因型患者比较,差异有统计学意义(P<0 .05);T/T基因型与C/C基因型患者比较,差异无统计学意义(P>0 .05)。胰岛素受体β亚基表达及血清黄体生成素、睾酮水平, 3种基因型患者比较,差异均无统计学意义(P>0 .05)。结论　PCOS患者胰岛素受体基因外显子17多态性在1008bp发生T→C的突变频率高于     

Apolipoprotein E and cholesteryl ester transfer protein polymorphisms in normal and preeclamptic pregnancies

OBJECTIVES: To evaluate the association of apolipoprotein (apo) E polymorphism and a cholesteryl ester transfer protein (CETP) polymorphism (CETP/TaqIB) with preeclampsia and with lipid/lipoprotein profile in pregnancy. MATERIALS AND METHODS: A group of 144 normal pregnant women (67 in the third trimester) were compared with 51 cases of preeclampsia in the third trimester of gestation. Apo E and CETP genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. Serum lipids, lipoproteins and apolipoproteins were evaluated using commercially available kits. LDL size was assessed by gradient gel electrophoresis. RESULTS: No differences were found in the distribution of subjects with respect to genotypes, in the apo E and CETP polymorphisms, between control and pathologic groups. In the third trimester of gestation (both control and case groups considered), apo E polymorphism, but not CETP polymorphism, was associated with different lipid and lipoprotein levels. Patients carrying the E2 allele (E2+) presented with significantly lower values of LDL cholesterol (LDLc) compared with carriers of E4 (E4+) and E3/3 individuals. E2+ also presented with the highest triglyceride (TG) level, although this was not statistically significant. On the other hand, HDL cholesterol (HDLc) and apo A-I levels were significantly reduced in E4+, compared with E3/3. Furthermore, E4+ presented with the highest total cholesterol and LDL and therefore LDLc/HDLc and apo B/apo A-I ratios were significantly higher in this group compared with the other two. CONCLUSIONS: Neither of our candidate genes showed association with preeclampsia. However, apo E genotype was associated with changes in lipid and lipoprotein profiles in pregnant women.     

Apolipoprotein E alleles in women with polycystic ovary syndrome

OBJECTIVE: To investigate the frequency of apoE alleles among women with polycystic ovary syndrome. DESIGN: Retrospective case-control study. SETTING: University-based endocrinology/infertility clinic. PATIENT(S): Healthy fertile women (n = 91) and women with a diagnosis of polycystic ovary syndrome (n = 58). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The presence of the three most common apoE alleles (epsilon2, epsilon3, and epsilon4) determined by polymerase chain reaction-restriction fragment length polymorphism in the two groups and in the general population in our area. RESULT(S): The frequency of the apo epsilon4 allele was 17.2% among women with polycystic ovary syndrome and was 18.7% among healthy fertile women, which is close to the rate in the general population in our area (19%). None of the apoE genotypes (Fisher's exact test; P=.71) or alleles (P=.78) was significantly overrepresented, and the homozygous genotype epsilon4 was not associated with the clinical disease. CONCLUSION(S): The observed profiles of allele and genotype frequencies confirm the equilibrium state between apoE polymorphism and polycystic ovary syndrome and suggest that apoE does not play a major role in the development of hyperlipidemia in the group of women with polycystic ovary syndrome.     

Steroidogenic acute regulatory protein (StAR) in the ovaries of healthy women and those with polycystic ovary syndrome

OBJECTIVE: Polycystic ovary syndrome is the most common cause of oligo-ovulation, affecting approximately 4% of women. A primary defect of steroidogenesis resulting in increased ovarian and adrenal androgen production may be responsible for polycystic ovary syndrome, at least in some patients. Because the action of the steroidogenic acute regulatory protein (StAR) initiates the process of steroidogenesis, we proceeded to test the hypothesis that increased production or concentration of StAR may result in the abnormality of steroidogenesis found in polycystic ovary syndrome. STUDY DESIGN: We examined the ovaries from 10 healthy women and 7 women with polycystic ovary syndrome, determining the relative concentration of StAR in total protein extracts by use of Western blotting, and the overall distribution and staining intensity of StAR in prepared tissue sections. RESULTS: Overall the ovaries of healthy women and women with polycystic ovary syndrome demonstrated a similar prevalence and size of follicular cysts, although the ovaries of women with polycystic ovary syndrome had a greater mean number of follicular cysts. In general, the distribution of StAR immunoreactivity within most of the ovarian structures was not different in the ovaries of women with polycystic ovary syndrome compared to those of the healthy ovaries. However, the ovaries from the cases demonstrated a significantly greater number of follicular cysts with staining for StAR immunoreactivity in the thecal cells than did the ovaries from healthy women (100% vs 38%, P <.05). CONCLUSION: These data suggest that the exaggeration in androgen biosynthesis in the ovaries of patients with polycystic ovary syndrome may be occurring at its earliest step (ie, that involving StAR), such that an increased amount of cholesterol is made available for androgen biosynthesis in the polycystic ovary.     

单侧多囊卵巢与多囊卵巢综合征的比较研究

目的:探讨单侧多囊卵巢的临床病理特点及病因。方法:收集单侧多囊卵巢12例,与8例典型多囊卵巢综合征对照比较,分析其临床表现、生化参数、卵泡液中相关激素水平以及卵巢间质细胞超微结构。结果:单侧PCO患者临床表现多样,和典型PCOS比较,单侧PCO出现月经改变和不孕显著减少。单侧PCO组血清PRL和T水平显著高于正常对照组,P<0.05;LH水平显著低于PCOS组,P<0.01。单侧PCO卵泡液中T和INS的水平比正常侧卵巢组显著升高,P<0.01;LH水平显著低于PCOS组,P<0.05。单侧PCO间质细胞粗面内质网、光面内质网不同程度出现扩张,部分粗面内质网有脱粒现象;线粒体出现扩张。结论:单侧PCO是一种不同于PCOS的特殊疾病类型,其临床表现多样,对卵巢生殖和内分泌功能的损害比PCOS轻。单侧PCO与PRL和卵巢局部T异常分泌均有关。单侧PCO间质细胞超微结构改变介乎正常卵巢和典型PC0S之间。     

A microsatellite polymorphism (tttta)n in the promoter of the CYP11a gene in Chinese women with polycystic ovary syndrome

A (tttta)n microsatellite polymorphism in the promoter of CYP11a gene was investigated in 201 Chinese Han women with polycystic ovary syndrome (PCOS) and 147 control women. The 6/6 genotype was defined with significant difference of CYP11a polymorphism between women with PCOS and control women, and associated with greater BMI in PCOS patients, suggesting a certain role of the six-repeat allele variant in the pathogenesis of Chinese women with PCOS.     

Role of the pentanucleotide (tttta)(n) polymorphism in the promoter of the CYP11a gene in the pathogenesis of hirsutism

OBJECTIVE: To determine if the (tttta)(n) repeat polymorphism in the promoter region of CYP11a gene is associated with hirsutism and hyperandrogenism in women from Spain. DESIGN: Controlled clinical study. SETTING: Tertiary-care institutional hospital. PATIENT(S): Ninety-two hirsute women and 33 healthy control women. INTERVENTION(S): Basal and adrenocorticotropin-stimulated serum samples and genomic DNA extracted and purified from whole-blood samples were obtained during the follicular phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): CYP11a (tttta)(n) repeat-polymorphism genotype and serum ovarian and adrenal androgen levels. RESULT(S): None of the CYP11a (tttta)(n) polymorphic alleles was associated with hirsutism. The absence of the four-repeat-units allele (4R-- genotype), which has been reported by other authors to be associated with polycystic ovary syndrome (PCOS), was found in 22.4% of the women studied here and was equally distributed among patients and controls, independently of the presence of PCOS and/or ovarian or adrenal hyperandrogenism. No differences were observed in serum hormone concentrations in 4R-- individuals as compared with subjects with at least one four-repeat-units allele. CONCLUSION(S): The (tttta)(n) repeat polymorphism in the promoter region of CYP11a does not appear to play any significant role in the pathogenesis of hirsutism and hyperandrogenism in women from Spain.     

A C/T single nucleotide polymorphism at the tyrosine kinase domain of the insulin receptor gene is associated with polycystic ovary syndrome

OBJECTIVE: To examine whether the insulin receptor (INSR) gene contributes to genetic susceptibility to the polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING: Academic endocrinology clinic. PATIENT(S): Ninety-nine women with PCOS as defined by the National Institutes of Health consensus and polycystic ovaries on ultrasonography, and 136 healthy controls. MAIN OUTCOME MEASURE: Frequency of genotypes of a single nucleotide polymorphism of the INSR gene in patients and controls. RESULT(S): After stratification of participants by body mass index, the frequency of the uncommon T allele of the INSR single nucleotide polymorphism was significantly increased in lean patients with PCOS (body mass index < or =27 kg/m2) compared with lean controls (relative risk, 2.1). CONCLUSION(S): The INSR gene is a susceptibility gene for PCOS among lean patients with PCOS. It remains to be determined whether the exon 17 C/T single nucleotide polymorphism is the susceptibility single nucleotide polymorphism for PCOS or whether it is in linkage disequilibrium with another INSR gene polymorphism.     

Lack of association between C-850T polymorphism of the gene encoding tumor necrosis factor-alpha and polycystic ovary syndrome.

In the present study, we determined whether genetic variability in the gene encoding tumor necrosis factor-alpha (TNF-alpha) contributes to individual differences in susceptibility to the development of polycystic ovary syndrome (PCOS). The study involved 87 Caucasian Finnish women with PCOS and 115 healthy control women who were genotyped for the C-850T polymorphism in the TNF-alpha gene promoter. Analysis by chi(2) was used to assess genotype and allele frequency differences between PCOS women and controls. A similar genotype distribution for the C-850T polymorphism was observed in the two groups, with the frequency of the variant T allele being 8.6% in the PCOS group and 9.6% in the control group (p = 0.862). Accordingly, the profile of genotype frequencies was similar in the groups. The observed profiles of allele and genotype frequencies confirm an equilibrium state between C-850T polymorphism and PCOS and suggest that polymorphism of the TNF-alpha gene is unlikely to contribute to the risk of PCOS.     

醛固酮合成酶基因多态性与多囊卵巢综合征相关性的研究

目的　探讨醛固酮合成酶 (CYP11B2 )基因多态性与多囊卵巢综合征 (PCOS)发病的关系。方法　采用聚合酶链反应、限制性内切酶消化及电泳技术 ,对 92例PCOS患者和 60例正常妇女的CYP11B2基因 3 44T位点基因多态性进行检测 ,并测定基础状态下促卵泡激素、促黄体生成素、雌二醇、睾酮、孕酮、泌乳素、血肾素活性、血管紧张素Ⅱ及醛固酮水平 ,比较不同基因型PCOS患者及正常妇女的肾素、血管紧张素、醛固酮及雄激素水平差异。结果　 ( 1)正常妇女、PCOS患者中 ,CYP11B2基因 3 44T位点C基因频率分别为 2 2 %和 3 6%。 ( 2 )PCOS患者T→C(TC、CC)出现率为 5 7% ,明显高于正常妇女的 3 7% (P <0 0 5 )。 ( 3 )PCOS患者CYP11B2基因型及基因频率的分布与正常妇女比较 ,差异有显著性 (P <0 0 5 ) ;CYP11B2基因 3 44TC、 3 44CC基因型的PCOS患者及正常妇女的肾素、血管紧张素、醛固酮及雄激素水平 ,均明显高于CYP11B2基因 3 44TT基因型者 (P <0 0 1)。结论　 ( 1)CYP11B2基因 3 44T位点变异 (T→C)的出现 ,可能增大了患PCOS的风险 ,并与PCOS发病有关。 ( 2 )CYP11B2基因 3 44CC、 3 44TC基因型可能是PCOS的易患基因型 ,并与PCOS患者肾素血管紧张素系统功能亢进有一定的关系