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  • 學位論文

肥胖婦女ADIPOQ基因多形性增加罹患多囊性卵巢症候群之危險

Polymorphism of the ADIPOQ gene increased the risk of polycystic ovary syndrome in obese women

指導教授 : 葉錦瑩

摘要


多囊性卵巢症候群(polycystic ovary syndrome; PCOS)是融合了內分泌、生殖及新陳代謝等功能障礙的症候群。也是育齡婦女中相當常見的疾病,盛行率約3-10%,臨床上常因為無排卵性不孕、月經不規則及雄性素過高的症狀而接受治療。 有50%以上的PCOS病患有程度不等的胰島素阻抗(insulin resistance; IR),而胰島素阻抗可能會造成葡萄糖耐受不良或第二型糖尿病。以往的研究發現,罹患多囊性卵巢症候群的婦女其體內脂締素(adiponectin)的濃度較低。本研究於某醫院生殖醫學中心召募研究對象並收集問卷及血液檢體,所有不孕症的病人中屬於多囊性卵巢的病人作為PCOS病例組,將其他不孕症病人作為Non-PCOS對照組,在同一個時間點進行研究,包括空腹血糖值、空腹胰島素、脂締素、各類脂質濃度以及ADIPOQ基因型的分析,並且探討其他可能影響多囊性卵巢症候群的危險因子,包含氧化壓力(脂質過氧化物質 MDA)、抗氧化程度(抗氧化物質Glutathione; GSH)、異常血脂、胰島素阻抗、高男性賀爾蒙之效應。 本研究中總共有404名研究對象,病例組有109人(27%),對照組有295人(73%)。病例婦女的平均年齡較輕,PCOS病例婦女的BMI、腰臀比、三酸甘油脂、總膽固醇、低密度膽固醇、體脂肪率都顯著高於對照組,而高密度膽固醇則是低於對照組。又PCOS病例有高男性荷爾蒙且有較低的SHBG(性荷爾蒙結合球蛋白);而低adiponectin濃度為胰島素阻抗的危險因子,但PCOS病例體內的adiponectin濃度則並未較對照組為低。 對於所有研究對象,ADIPOQ基因多形性與PCOS的發生沒有顯著相關。但在BMI≧24的肥胖婦女身上,ADIPOQ基因在+276位點上攜帶G/T基因型者有顯著PCOS發生的危險性,危險對比值為3.2倍(95% CI:1.22-8.36)。BMI可能為PCOS與ADIPOQ基因多形性間的干擾因子,而ADIPOQ基因在+276位點攜帶G/G基因型者其adiponectin濃度會顯著較低。 PCOS患者其體內的氧化壓力(MDA)、抗氧化壓力(GSH)與對照組並沒有顯著差異。胰島素阻抗、月經異常、低SHBG為PCOS發生的危險因子,而氧化壓力及生活習慣對於PCOS沒有顯著影響。

並列摘要


Polycystic ovary syndrome (PCOS) is associated with infertility and metabolic disorders. PCOS is the common endocrinopathy affecting women of reproductive age, that is characterized by amenorrhrea,hyperandrogenism. Over 50% of PCOS women have insulin resistance (IR) and may induce glucose intolerance or type II diabetes in future. Previous studies found that PCOS women had lower concentrations of adiponectin. All subjects were recruited from Reproductive Medicine Centre, we collected questionnaires and blood samples from all women who infertility (PCOS patients as case group and remaining Non-PCOS patients as control group). The measures including fasting glucose, fasting insulin, adiponectin, lipid concentration and ADIPOQ gene polymorphism were determinated. Other risk factors which may affect PCOS, including oxidative stress (MDA), anti-oxidation (Glutathione; GSH), dyslipidemia, insulin resistance and hyperandrogenemia,were detected. A total of 404 subjects participated in this study, including 109 women for case group, 295 women for control group.PCOS women were younger than control group;BMI, waist-hip ratio, triglyceride, total cholesterol, LDL-C, body fat ratio of PCOS women were higher than the control group significantly, but HDL-C is lower . PCOS women have high testosterone and low SHBG (sex hormone binding globulin) level, but adiponectin levels was not lower than the control group significantly in this study. For all women , the ADIPOQ gene polymorphism was not associated with PCOS .But in the obese women(BMI≧24),who with the G/T genotype at ADIPOQ gene position 276 had a higher risk for PCOS than those with T/Tgenotype (OR=3.2 ,95%CI:1.22-8.36).BMI may be a confounding factor between PCOS and ADIPOQ gene polymorphism.Women with G/G genotype at position 276 had lower adiponectin concentration significantly. Oxidative stress (MDA) and antioxidation (GSH) were not different between the case group and control group. Insulin resistance, abnormal menses, low SHBG were risk factors for PCOS; oxidative stress, antioxidation and living habits did not affect PCOS .

參考文獻


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