APLN基因多型性與代謝症候群之相關性以及TNF-α藥物治療下APLN的變化

The association of APLN polymorphisms with metabolic syndrome and the change of APLN gene expression treated with TNF-α

李依寧(Yi-Ning Li)

指導教授 ： 卓夙航

高雄醫學大學/醫學院/醫學遺傳學研究所/碩士(2009年)

摘要

背景
脂肪激素不正常的分泌在發展成代謝症候群與心血管疾病佔有一席之地。Apelin是近年被發現有脂肪激素功能，因明顯受到胰島素與肥胖的調控而增加表現。不管是在人體或小鼠脂肪組織發現到內生性腫瘤壞死因子-α（Tumor necrosis factor-alpha, TNF-α）與apelin有高度的相關性。故本研究探討apelin基因多型性與代謝症候群的相關性，另外，偵測在人體初代細胞培養中TNF-α藥物處理後，apelin基因表現是否因性別而有差異。
方法
本研究樣本來自高雄醫學大學附設醫院健康檢查中心，根據美國國家膽固醇教育計畫成人治療顧問群第三次會議修正亞洲版代謝症候群定義，有三項或三項以上危險因子者當作有代謝症候群者，無任何危險因子或一項者當作無代謝症候群者，選出apelin四個標的基因多型性（tagging SNPs， tSNPs）進行實驗。收集臨床病人腹部脂肪組織，培養出脂源性間葉幹細胞誘導生成成熟脂肪細胞後，經過TNF-α藥物處理偵測apelin基因表現情形。
結果
本研究中，共有498位有代謝症候群者，1311位無代謝症候群者，男性佔51.4％平均年齡51.1 ?b 13.55歲，我們發現代謝症候群與apelin四個標的單核?˙襤穧]多型性沒有統計上顯著意義，故進一步分析基因多型性與五項危險因子的相關性。SNP 3在腹部肥胖（校正年齡、隱性模式，p = 0.023）和空腹血糖值（校正年齡、顯性模式，p = 0.002）以及SNP 4在腹部肥胖（校正年齡、顯性模式，p = 0.026）有統計上意義。10 ng/ml TNF-α藥物治療1小時，在性別上有統計上顯著的意義（p = 0.028）。
結論
本研究顯示apelin基因多型性會影響腹部肥胖與胰島素抗阻性形成代謝症候群；經由尋找代謝症候群的易感性基因，能更深入瞭解其致病機轉。

關鍵字

代謝症候群 ； 基因多型性 ； 肥胖 ； 胰島素抗阻性 ； 肥胖細胞激素 ； 脂泌素 ； 脂肪

並列摘要

Background and Purpose
Dysregulation of the production of adipokines plays a pivotal role in the development of metabolic syndrome and cardiovascular comorbidity. Apelin , a newly identified adipokine, is novel up-regulated by insulin and obesity. The endogenous expression of Tumor necrosis factor-alpha (TNF-α) was reported a high correlation with apelin in adipocyte of human and rat. The purpose of present study is to investigate whether the polymorphisms at the gene encoding apelin confer risks for metabolic syndrome. The effect of TNF-α on expression of apelin will be also investigated.
Methods
The study subjects are volunteers who received health exam at the Kaohsiung Medical University Hospital. The diagnosis of metabolic syndrome is based on the modified version of National Cholesterol Education Program Adult Treatment Panel Ⅲ. We conducted a case-control association study using subjects with at least three of the five components of metabolic syndrome as cases and those with zero or one feature as controls. Four tagging SNPs at apelin gene were genotyped. We gathered clinical patients’ adipocyte primary cell culture. Isolated human adipose tissue-derived mesenchymal stem cells were induced to mature adipocyte then treated with TNF-α to measure apelin expression.
Results
A total of 498 cases and 1311 controls were included in the present study. Men were accounted for 51.4 % and the average age was 51.1 ?b 13.55 year-old. The four SNPs at the apelin gene were not statistically associated with metabolic syndrome. We further evaluated the apelin genetic effect on each of the five components of metabolic syndrome. SNP 3 appeared to be accounted for abdominal obesity (p = 0.023, adjusted age recessive model) and fasting glucose (p = 0.002, adjusted age dominant model). SNP 4 appeared to be accounted for abdominal obesity (p = 0.026, adjusted age dominant model). Apelin gene expression after 10 ng/ml TNF-α treated 1hour was significant different between sexual effect (p = 0.028).
Conclusions
The present study demonstrated that polymorphisms at the apelin gene may influence abdominal obesity and insulin resistance to the development of metabolic syndrome.

並列關鍵字

metabolic syndrome ； polymorphisms ； obesity ； insulin resistance ； adipocytokine ； adipokine ； adipocyte

參考文獻

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