多囊性卵巢症候群是婦女常見的內分泌疾病，在遺傳上的研究則發現多囊性卵巢症候群的病人在胰島素接受器的基因多型性及其表現程度可能有異常，才會導致病症的發生。其中可以發現胰島素接受器受質蛋白質的增加或改變(IRS-1)以及胰島素接受器受質的基因多型性變異(Gly972Arg在IRS-1)都會造成多囊性卵巢症候群的病人有胰島素阻抗現象發生及慢性發炎反應。本研究的目的是希望藉由藥物基因體醫學的方法來探討胰島 素接受器受質的基因多型性變異對多囊性卵巢症候群患者在接受胰島素增敏劑美佛明藥物治療的反應及對胰島素抗性血清可溶性細胞粘附分子含量的影響與慢性發炎反應指標。
本研究的方法，首先收集30位多囊性卵巢症候群患者及20位正常患者之血液檢體，經由生化指標檢測分析，口服葡萄糖耐受性測驗分析及分子基因學研究。其中多囊性卵巢症候群組分成(1)IRS-1基因多型IRS-1(Gly/Arg)15位及(2)IRS-1基因多型性IRS-1(Gly/Gly)15位，利用酵素連結免疫分析，探討接受胰島素增敏劑美佛明藥物治療前後的胰島素抗性血清可溶性細胞粘附分子的含量。
目前30位多囊性卵巢症候群患者服用美佛明(metformin)後，發現IRS-1(Gly/Arg)中體重在治療前63.70 ± 14.00 kg與治療後62.12 ± 13.76 kg有明顯改善，在IRS-1(Gly/Arg)中胰島素抗性指標HOMA-IR中，治療前10.21±10.72治療後為4.44±2.86，有明顯改善。另外IRS-1(Gly/Gly)發炎反應指標中血管細胞黏附分子-1(soluble vascular adhesion molecule-1 sVCAM-1)治療前421.81±133.68 ng/ml與治療後331.32±118.31ng/ml有明顯改善。發炎指標是評估心血管疾病風險之重要因數，因為發炎在動脈粥狀硬化形成過程中扮演著重要角色與新陳代謝症候群的組成分多寡有正相關性，所以在臨床上可用來預估偵測未來糖尿病的發生及預防心血管方面之疾病。這結果證實多囊性卵巢症候群患者在接受胰島素增敏劑美佛明藥物治療的反應是有效果的。而不同IRS基因多型性的情況存在與否是否有改變，則需要更多個案收集後再分析。 Polycystic ovary syndrome (PCOS) is a common endocrinologic disease in women. It will increase the risks of cardiovascular disease, insulin resistance and diabetes. The symptoms are including hyperinsulinemia, ovulatory dysfunction, hyperandrogenism, infertility and abortion. At present, the first line treatment for PCOS is the use of insulin sensitizer or combined with clomiphene. The studies about the use of metformin in PCOS are well-documented, recently. In addition, metformin will improve the severity of metabolic syndrome and decrease the complication. In genetic study, there are gene polymorphism in insulin receptor that will result in the occurrence of this disease, especially in the change of insulin receptor substrate-1 (IRS-1). The polymorphism in IRS-1 (Gly972Arg) will lead to the occurrence of insulin resistance, and type II diabetes and reflect low-grade chronic inflammation. The laboratory data in women with PCOS demonstrated several significant changes: (1)(Gly/Arg) group of Body weight : pre-tx 63.70 ± 14.00 kg, post-tx 62.12 ± 13.76 kg; (2)(Gly/Arg) group of the HOMA-IR: pre-tx 10.21±10.72,post-tx 4.44±2.86，(3)(Gly/Gly) group of the soluble vascular adhesion molecule-1 (sVCAM-1), the marker of low-grade chromic inflammation, decreased significantly from pre-tx421.81±133.68 decrease to post-tx 331.32±118.31(ng/ml). Elevated serum levels of sVCAM-1 has been associated with the severity of insulin-resistant states, and the higher level of sVCAM-1 might increase the risk of diabetes and potentially changes those may lead to cardiovascular disease. Herein, in this study we have distinguished these different phenotypes on the basis of their endocrine and metabolic features and their circulating markers of CV risk, and correlate to IRS-1 polymorphism. The results showed the benefits of using metformin to PCOS patients. It still needs more cases to clarify the relationship between IRS gene polymorphism after metformin use in PCO women.
