1型糖尿病一级亲属胰岛自身抗体与HLA-DQ基因型的关系  

Relationship between islet autoantibodies and HLA-DQ genotypes in first-degree relatives of autoimmune type 1 diabetes

作　　者：王建平[1,2] 周智广[1] 黄干[1] 袁颖[1] 周海峰[1] 侯粲[1] 杨亚玲[1] 

机构地区：[1]中南大学湘雅二医院内分泌科,中南大学糖尿病中心,中南大学代谢内分泌研究所,长沙410011 [2]南华大学附属第二医院内分泌科

出　　处：《中华内分泌代谢杂志》2007年第5期410-415,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：卫生部优秀青年科技人才专项基金(Q9420);湖南省科技厅重点项目(03SSY1009)

摘　　要：目的探讨1型糖尿病一级亲属谷氨酸脱羧酶抗体(GADA)、蛋白酪氨酸磷酸酶抗体(IA- 2A)、胰岛素自身抗体(IAA)与HLA-DQ基因型之间的关系。方法横断面、病例对照研究。采用放射配体法检测351例糖耐量正常的1型糖尿病一级亲属与376名正常对照者GADA、IA-2A与IAA。其中156例自身免疫1型糖尿病一级亲属与278名正常对照采用PCR-直接测序法明确HLA-DQ基因型。结果(1)与正常对照比较,1型糖尿病一级亲属DQA1*03、DQB1*0303、*0401等位基因与DQA1*03-DQB1 *0303、DQA1*05-DQB1*0201、DQA1*03-DQB1*0401单体型频率增高(均P<0.05或P<0.01),而DQA1*0601、*0201和DQB1*0301、*0602等位基因与DQA1*0102-DQB1*0602单体型频率减少(均P<0.05或P<0.01)。(2)与1型糖尿病患者比较,1型糖尿病一级亲属DQA1*03等位基因频率减少(45.8%vs 54.5%,P<0.05)。(3)携带DQA1*03-DQB1*0303单体型者,GADA、IA-2A与IAA任一自身抗体阳性率高于不携带此单体型者(23.0%vs 8.6%,P<0.05)。结论携带DQA1*03-DQB1*0303单体型的一级亲属,GADA、IA-2A与IAA任一自身抗体检出率最高。Objective To evaluate the association of islet autoantibodies [ glutamic acid decarboxylase antibody （GADA）, protein tyrosine phosphatase antibody （IA-2A） and insulin autoantibodies （IAA） ] with HLA-DQ genotypes in the first-degree relatives of autoimmune type 1 diabetes mellitus. Methods This was a crosssectional and case-control study. Three hundred and fifty-one first-degree relatives with normal glucose tolerance of patients with type 1 diabetes mellitus and 376 healthy controls were recruited and measured for GADA, IA-2A and IAA by radioligand assay, and 156 first-degree relatives of patients with autoimmune type 1 diabetes mellitus and 278 controls were typed for genetic polymorphisms of HLA-DQ with PCR sequencing-based typing method. Results （ 1 ） DQA1 ＊ 03, DQB1 ＊ 0303, ＊ 0401 alleles and DQA1 ＊ 03-DQB1 ＊ 0303, DQA1 ＊ 05-DQB1 ＊ 0201, DQA1 ＊ 03-DQB1 ＊ 0401 haplotypes were significantly increased in the first-degree relatives of autoimmune type 1 diabetes mellitus （P 〈0.05 or P 〈0.01）, but DQA1 ＊ 0601, ＊ 0201, DQB1 ＊ 0301, ＊ 0602 alleles and DQA1 ＊ 0102-DQB1 ＊ 0602 haplotype were significantly decreased （ P 〈 0.05 or P 〈 0.01 ）. （ 2 ） The frequency of DQA1 ＊03 allele in the first-degree relatives was lower than that in their probands （45.8% vs 54.5%, P 〈 0.05）. （3） GADA, IA-2A or IAA were more frequent in first-degree relatives with DQA1 ＊ 03-DQB1 ＊ 0303 haplotype than those without this haplotype （23.0% vs 8.6%, P 〈 0.05）. Conclusion First-degree relatives with DQA1 ＊ 03-DQB1 ＊ 0303 haplotype are easy to express autoantibodies GADA, IA-2A or IAA.

关 键 词：糖尿病 1型 一级亲属 HLA基因型 胰岛自身抗体 

分 类 号：R587.1[医药卫生—内分泌]