砷暴露地區居民血糖代謝基因多形性與糖尿病盛行情形之相關研究
本研究目的在探討糖尿病盛行率與葡萄糖激脢 (Glucokinase, GCK) 、磺醯脲受體 (Sµlph onylurea receptor, SUR1) 、血管收縮素轉化脢 (Angiotensin-converting enzyme, ACE) 之 基因多形性及無機砷暴露的相關性以瞭解無機砷致糖尿病的機轉。本研究以民國八十年 在蘭陽盆地所建立之追蹤世代及民國八十六年起，此一世代接受追蹤訪視者，共計 514 6 人為研究母群。研究對象選取合乎糖尿病患條件且有檢體者為病例組共 137 人，以年 齡、性別配對健康對照 137 人，共 274 人。磺醯脲受體、血管收縮素轉化脢之基因以聚 合脢連鎖反應 (Polymerase Chain Reaction, PCR) 進行 DNA 增幅，接著進行限制片段長 度多形性 (Restriction Fragment Length Polymorphism, RFLP) 作基因多形性檢查；葡萄糖 激脢為微衛星小體基因標記，含氮鹼基 (CA) 重複序列次數不同，具有高度多形性，以 聚合脢連鎖反應 (PCR) 進行 DNA 增幅，以 ABI PRISM® 310 Genetic Analyzer 測序儀定 序，觀察 DNA 的序列是否有多出的情形。結果發現，身體質量指數 >24.0 、三酸甘油 脂較高者及高血壓患者有顯著較高的罹患糖尿病危險性，運動對於糖尿病有保護作用；
葡萄糖激脢、磺醯脲受體基因多形性分佈在糖尿病患者及健康對照組間未有顯著差異。
不過， SUR1 exon16 nt-3 為 vw 或 vv 且 SUR18 codon759 為 vw 者，有較高的糖尿病罹 病危險性；血管收縮素轉化脢帶缺失對偶基因 (ID&DD) 者有顯著較高的罹患糖尿病危 險性；本研究結果並未能發現慢性砷暴露會顯著增加研究族群罹患糖尿病危險性； GC K1 及 ACE 基因交互作用對於罹病危險性有顯著的增加，又加入砷暴露交互作用下，在 低砷暴露時還是可以看到此二個基因對糖尿病罹病危險性的顯著影響。
關鍵字：砷、糖尿病、基因多形性、葡萄糖激脢、磺醯脲受體、血管收縮素轉化脢
The Association between Genetic Polymorphisms of Blood Sugar Metabolism Genes and Diabetes Mellitus among Residents in
Arseniasis
The specific aim of this study is the association between the prevalence of diabetes mellitus an d genetic polymorphysims of glucokinase(GCK),sulphonylurea receptor(SUR1) and angiotens in-converting enzyme(ACE).A total of 137 residents of Lang-yang Basin who had diabetes me llitus(DM) history or whose physical examination reports with fasting sugar level 140 mg/dl ≧ were recruited as DM.Another 137 age-sex-matched non-DM control residents were also recru ited.Genetic polymorphisms of SUR1 and ACE were examined by PCR and RFLP.GCK1 is a kind of microsatellite marker which is a type of dinucleotide(CA)n repeat polymorphisms and is highly polymorphic in human population.ABI 310 sequencer was used to examined genetic polymorphysims of GCK1.Logistic regression model was used to estimate risks of DM induce d by various risk factors and their 95 wnfidence intervals.﹪
The result shows that:(1)People with BMI>24.0 or with higher serum triglyceride or with hype rtension history have the significantly higher risk of DM.(2)Study subjects who have regular e xercise habits have lower risk of DM.(3)The subjects with D allele of ACE marker have highe r risk of DM.(4)Non-significantly higher risk of DM induced by various genetic polymorphis ms of SUR1 and GCK were observed.(5)Chronic arsenic exposure didn’t increased risk of pre valence of DM among the subjects.(6)The syneristic effert between chronic arsenic exposure a nd genetic polymorphysims on risk of DM did not observed in this study.
Keywords ： Arsenic, Diabetes mellitus, Polymorphysim, Glucokinase, Sulphonylurea recept er, Angiotensin-converting enzyme
