脂締素、腫瘤壞死因子-alpha -308基因多形性與台灣人代謝症候群發生之效應

Effects of adiponectin and tumor necrosis factor-alpha -308 genetic polymorphism on the development of Taiwanese metabolic syndrome

王俊堯(Jiun-Yao Wang)

指導教授 ： 翁瑞宏

中山醫學大學/醫學院/醫學研究所/碩士(2012年)

https://doi.org/10.6834/CSMU.2012.00033

摘要

脂肪組織分泌的脂締素 (adiponectin) 被建議可增加脂肪酸的氧化以影響體內胰島素 (insulin) 敏感性，腫瘤壞死因子-alpha (tumor necrosis factor [TNF-alpha]) 亦被指出會干擾胰島素與胰島素接受器結合，阻斷訊息傳遞而導致胰島素阻抗 (insulin resistance) 的發生。脂締素與TNF-alpha兩者皆可能參與代謝症候群 (metabolic syndrome [MetS]) 之發展，因此我們設計一項以社區為基礎的研究來探討脂締素 (apM1) 基因、TNF-alpha基因與MetS發生之關係。總計，330名研究對象被納入本研究，其中有121名 (36.7%) 符合MetS之定義。問卷被執行以取得個人特徵資料，每名對象之身體測量、血壓與生化指標也被評估，apM1 T45G以及TNF-alpha G-308A基因型是以聚合酶鏈鎖反應 (polymerase chain reaction) 來進行判定。在調整干擾因子之效應後，結果顯示收縮壓 (systolic blood pressure) >= 130 mmHg或舒張壓 (diastolic blood pressure) >= 85 mmHg者、身體質量指數 (body mass index [BMI]) > 27 kg/m2者、三酸甘油酯 (triglyceride) >= 150 mg/dL者、較低的高密度脂蛋白膽固醇 (high density lipoprotein-cholesterol [HDL-C]) 濃度者、空腹血糖濃度 >= 110 mg/dL者、與胰島素濃度 >= 15.6 uU/mL者皆分別相較於正常數值者有顯著增加的MetS發生危險性。在BMI > 27 kg/m2者中，攜帶apM1 +45 G對偶基因者相較於攜帶TT基因型者具有0.40倍 (95% confidence interval [C.I.] = 0.16-0.99) 的MetS發生危險性。同樣地在HDL-C異常者中，apM1 +45 G對偶基因攜帶者相較於TT基因型攜帶者，也呈現顯著較低的MetS發生危險性 (危險對比值 [odds ratio] = 0.42; 95% C.I. = 0.19-0.95)。進一步地，在呈現血壓正常之apM1 +45 TT基因型攜帶者中，TNF-alpha -308 A對偶基因也相較於GG基因型有顯著較高的MetS發生危險性，並且也具有顯著較高的異常血糖危險性。因此，我們的結果建議著攜帶apM1 +45基因變異者是較可能發展出MetS。

關鍵字

脂締素 ； 胰島素 ； 腫瘤壞死因子-alpha ； 代謝症候群 ； 血糖

並列摘要

Adiponectin, secreted by adipose tissue, has been suggested to affect insulin sensitivity in the body by increasing fatty acid oxidation. Tumor necrosis factor-alpha (TNF-alpha) was also pointed out that would interfere with the binding of insulin and insulin receptor, block the signal transduction and lead to the occurrence of insulin resistance. Both of adiponectin and TNF-alpha may be involved in the development of the metabolic syndrome (MetS). Therefore, we designed a community-based study to investigate the relationship of adiponectin (apM1), TNF-alpha and the occurrence of MetS. A total of 330 study subjects were recruited in our study, 121 (36.7%) met the definition of MetS. A questionnaire was administered to obtain data of personal characteristics. Anthropometry, blood pressure and biochemical indicators were assessed in each subject. The apM1 T45G and TNF-alpha G-308A genotypes were identified by the polymerase chain reaction. After adjusting the effects of confounding factors, results showed that individuals with systolic blood pressure >= 130 mmHg or diastolic blood pressure >= 85 mmHg, body mass index (BMI) > 27 kg/m2, triglyceride >= 150 mg/dL, lower level of high density lipoprotein-cholesterol (HDL-C), fasting glucose >= 110 mg/dL, and insulin level >= 15.6 uU/mL had significantly increased risk for MetS development than those with normal indices, respectively. Among subjects with BMI > 27 kg/m2, those carrying apM1 +45 G allele had a 0.40-fold risk (95% confidence interval [C.I.] = 0.16-0.99) for MetS development than those carrying TT genotype. Similarly, among subjects with abnormal HDL-C, apM1 +45 G allele carriers compared to TT genotype carriers also had a lower risk for MetS occurrence (odds ratio = 0.42; 95% C.I. = 0.19-0.95). Furthermore, among apM1 +45 TT genotype carriers who experienced normal blood pressure, TNF-alpha -308 A allele compared to GG genotype had a significantly higher risk of MetS development, and those also had a significantly higher risk of abnormal blood glucose. Therefore, our findings suggested that individuals possessing apM1 +45 genetic variants were more likely to develop MetS.

並列關鍵字

Adiponectin ； insulin ； tumor necrosis factor-alpha ； metabolic syndrome ； blood glucose

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