腸病毒可能誘發第一型糖尿病

ID 53837 Subject/Title Comparison of Nucleotide Sequence of p2C Region in Diabetogenic and Non-Diabetogenic Coxsackie Virus B5 Isolates Alternative Title 引致與非引致糖尿病之克沙奇B5病毒株其p2C核酸序列之比較 Author 周正忠(Cheng-Chong Chou);林貴香(Kuei-Hsiang Lin);柯冠銘(Guan-Ming Ke);董宜青(Yi-Ching Tung);趙美琴(Mei-Chyn Chao);鄭貞英(Jeng-Yin Cheng);陳百薰(Bai-Hsiun Chen) Journal Title The Kaohsiung Journal of Medical Sciences Vol./Publishing Date 20卷11期 (2004/11) Page(s) 525-532 Language 英文 Abstract 腸 病毒是導致第一型糖尿病病因之環境促發因子，B群克沙奇病毒其2C蛋白中有六個胺基酸序列(PEVKEK)與第一型糖尿病之主要自體免疫抗原：麩胺酸脫羧 酵素(65GAD)之序列相同。從1995至2002年吾人從南台灣收集22株克沙奇B5病毒，其中四株來自於四例新發作第一型糖尿病病人，另收集已發表 原型2株。所有22株克沙奇B5病毒株皆以免疫螢光及中和試驗鑑定確認。吾人比較22株引致關第一型糖尿病和非引致糖尿病克沙奇B5病毒株其2C蛋白 300個核酸序列，結果發現南台灣22株克沙奇B5病毒核酸序列僅有0.3-10%之相異性。四例第一型糖尿病病人克沙奇B5病毒核酸甘序列僅有2.4- 3.4%之相異性。此南台灣22株克沙奇B5病毒與已發表克沙奇B5病毒原型珠2C蛋白核酸序列比較顯示有18.4-24.1%之差異。除了96- 1214病毒株外，所有其他與糖尿病相關及非糖尿病之病毒株2C蛋白亦皆含有PEVKEK。本研究顯示南台灣22株克沙奇B5病毒核酸序列有高度的相似 性，引致與非引致糖尿病之克沙奇B5病毒株應無不同，吾人認爲第一型糖尿病之病因中其他因素，如HLA基因易致病性及自體免疫抗體可能亦扮演重要之角色。 Enteroviruses are environmental triggers in the pathogenesis of type 1 diabetes mellitus (DM). A sequence of six identical amino acids (PEVKEK) is shared by the 2C protein of Coxsackie virus B and the glutamic acid decarboxylase (GAD) molecules. Between 1995 and 2002, we investigated 22 Coxsackie virus B5 (CVB5) isolates from southern Taiwan. Four of these isolates were obtained from four new-onset type 1 DM patients with diabetic ketoacidosis. We compared a 300 nucleotide sequence in the 2C protein gene (p2C) in 24 CVB5 isolates (4 diabetogenic, 18 non-diabetogenic and 2 prototype). We found 0.3-10% nucleotide differences. In the four isolates from type 1 DM patients, there was only 2.4-3.4% nucleotide difference, and there was only 1.7-7.1% nucleotide difference between type 1 DM isolates and non-diabetogenic isolates. Comparison of the nucleotide sequence between prototype virus and 22 CVB5 isolates revealed 18.4-24.1% difference. Twenty-one CVB5 isolates from type 1 DM and non-type 1 DM patients contained the PEVKEK sequence, as shown by the p2C nucleotide sequence. Our data showed that the viral p2C sequence with homology with GAD is highly conserved in CVB5 isolates. There was no difference between diabetogenic and non-diabetogenic CVB5 isolates. All four type 1 DM patients had at least one of the genetic susceptibility alleles HLA-DR, DQA1, DQB1. Other genetic and autoimmune factors such as HLA genetic susceptibility and GAD may also play important roles in the pathogenesis in type 1 DM. Keyword(s) 核酸序列定序,克沙奇B5病毒,第一型糖尿病;nucleotide sequence,Coxsackie virus B5,type 1 diabetes mellitus CEPS Category Subject Catagory>Medical & Life Science>Medicine