摘要
目的探讨急性起病1型糖尿病(T1DM)患者谷氨酸脱羧酶抗体(GADA)、蛋白酪氨酸磷酸酶抗体(TA-2A)、胰岛素自身抗体(IAA)与人类白细胞抗原(HLA-DQ)基因型之间的关系。方法采用横断面、病例对照研究方法,495例 T1DM 患者与376例正常对照用放射配体法检测GADA 和 IA-2A,其中使用胰岛素在2周以内的71例患者与300例正常对照检测 IAA。187例抗体阳性、151例抗体阴性 T1DM 患者与278例正常对照采用 PCR 直接测序法确定 HLA-DQ 基因型。结果(1)与正常对照比较,T1DM 患者(n=187)DQA1*03-DQB1*0303、DQA1*05-DQB1*0201与 DQA1*03-DQB1*0401单体型频率增高(分别为32.6% vs 21.9%,14.1% vs 3.5%与10.2% vs 2.9%,均P<0.01),DQA1*0102-DQB1*0602单体型频率降低(1.7% vs 5.3%,P<0.05),而 DQA1*03-DQB1*0302频率差异无统计学意义(4.7% vs 3.8%,P>0.05)。(2)在338例 T1DM 患者中,携带DQA1*05-DQB1*0201与 DQA1*03-DQB1*0401单体型患者,GADA 阳性率高于不携带此单体型者(分别为55.8% vs 41.0%与65.5% vs 40.3%,P<0.05或 P<0.01);携带 DQA1*03-DQB1*0303单体型患者 IA-2A 阳性率高于不携带此单体型者(27.0% vs 7.9%,P<0.01);携带 DQA1*03-DQB1*0302单体型患者 GADA 与 IA-2A 阳性率分别与不携带此单体型者比较,差异均无统计学意义(48.5% vs 43.9%与24.2% vs 15.4%,P>0.05);而携带保护性 DQA1*0102-DQB1*0602单体型患者 GADA 阳性率低于不携带此单体型者(16.7% vs 45.9%,P<0.05)。携带易感单体型者 IAA 检出率与不携带者比较,差异均无统计学意义(P>0.05)。结论 1型糖尿病患者 GADA 与 DQA1*05-DQB1*0201、DQA1*03-DQB1*0401单体型相关,IA-2A 与 DQA1*03-DQB1*0303单体型相关。
Objective To explore the relationship between the 3 islet autoantibodies, i. e., glutamic acid decarboxyase antibody （ GADA）, protein-tyrosine-phosphatase-2 autoantibody （ IA-2A）, and insulin autoantibody （ IAA）, and human leukocyte HLA-DQ genotypes in the patients with type 1 diabetes mellitus （T1DM ）. Methods Peripheral blood samples were collected from 495 T1DM patients and 376 healthy controls. Radioligand assay was used to detect the levels of GADA and IA-2A. Seventy-one of the 495 T1DM patients with insulin treatment less than 14 days underwent radioligand assay to measure the IAA level. 338 TIDM patients, including 187 antibodies-positive and 151 antibodies-negative patients, and 278 healthy controls underwent PCR and sequencing so as to examine the genetic polymorphism of HLA-DQ. Results （1） The frequencies of DQA1 ＊ 03-DQB1 ＊ 0303, DQA1 ＊ 05-DQB1 ＊ 0201, and DQA1 ＊ 03- DQB1 ＊ 0401 haplotypes in the T1DM patients were 32. 6%, 14. 1% and 10. 2% respectively, all significantly higher than those in the controls （21.9%, 3.5%, and 2.9% respectively, all P 〈 0.01 ）, however, the frequency of DQA1 ＊ 0102-DQB1 ＊ 0602 haplotype in the T1DM patients was 1. 7%,significantly lower than that in the controls （5.3 %, P 〈 0.05 ）. （2） The GADA positive rates of in the T＇DM patients with DQA1 ＊ 05-DQB1 ＊ 0201 or DQA1 ＊ 03-DQB1 ＊ 0401 haplotype were 55.8% and 65.5% respectively, both significantly higher than those of the T1DM patients without DQA1 ＊ 05-DQB1 ＊ 0201 or DQA1 ＊ 03-DQB1 ＊ 0401 haplotype （41.0% and 40.3%, respectively P 〈0.05 or P 〈0.01 ）, and the IA- 2A positive rate of the T1DM patients with DQA1 ＊ 03- DQB1 ＊ 0303 haplotype was 27.0%, significantly higher than that of the T1DM patients without DQA1 ＊ 03- DQB1 ＊ 0303 haplotype （7.9%, P 〈 0.01 ）, there were no significant differences in GADA and IA-2A positivity between the T1DM patients with and without DQA1 ＊ 03-DQB1 ＊ 0302 haplotype （48.5% vs 43.9% and 24.2% vs 1
出处
《中华医学杂志》
CAS
CSCD
北大核心
2007年第34期2380-2384,共5页
National Medical Journal of China
基金
卫生部优秀青年科技人才专项基金(Q9420)
湖南省科技厅重点资助项目(03SSY1009)
