Islet autoantibodies are associated with HLA-DQ genotypes in Han Chinese patients with type 1 diabetes and their relatives
Islet autoantibodies are associated with HLA-DQ genotypes in Han Chinese patients with type 1 diabetes and their relatives
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中国汉族 1 型糖尿病患者及其亲属的胰岛自身抗体与 HLA-DQ 基因型相关
DOI：
10.1111/j.1399-0039.2007.00916.x
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发表时间：
2007-11-01
期刊：
影响因子：
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通讯作者：
Hagopian, W. A.
中科院分区：
文献类型：
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作者：
Wang, J.-P.;Zhou, Z.-G.;Hagopian, W. A.
本研究的目的是探讨1型糖尿病（T1D）患者及其一级亲属（FDR）的谷氨酸脱羧酶胰岛自身抗体（GADA）、胰岛抗原2A（IA-2A）、胰岛素自身抗体（IAA）和人类白细胞抗原（HLA）-DQ基因型之间的关系。横断面和病例对照研究。招募了汉族人群中的 495 名 T1D 患者、419 名 FDR 和 376 名对照受试者并进行了 GADA 和 IA-2A 检测，同时对 71 名病例、所有 FDR 和 300 名对照受试者进行了 IAA 检测。采用基于聚合酶链反应测序的方法对 338 名 T1D 患者（包括 187 名抗体阳性患者和 151 名抗体阴性患者）、173 名 FDR 和 278 名对照者进行 HLA-DQ 基因分型。与对照相比，DQA1*03-DQB1*0303、DQA1*05-DQB1*0201和DQA1*03-DQB1*0401单倍型频率较高（P < 0.05-0.01），而DQA1*0102-DQB1*0602单倍型频率较低（P < 0.01）。 T1D 患者。 FDR 中的 DQA1*03 等位基因少于先证者 (P < 0.05)。 GADA 在携带 DQA1*05-DQB1*0201 或 DQA1*03-DQB1*0401 单倍型的 T1D 患者中更为常见（55.8% vs 41.0%、65.5% vs 40.3%，P < 0.05-0.01），而 IA-2A 在携带 DQA1*03-DQB1*0401 单倍型的患者中更为常见。 DQA1*03-DQB1*0303 单倍型（27.0% vs 7.9%，P < 0.05-0.01），GADA 和 IA-2A 在 DQA1*03-DQB1*0303/DQA1*05-DQB1*0201 单倍型患者中均频繁出现（34.5% vs 9.7%，P < 0.01）。 DQA1*0102-DQB1*0602 单倍型患者的 GADA 阳性率较低（16.7% vs 45.9%，P < 0.05）。具有和不具有易感 DQ 单倍型的患者之间 IAA 的频率没有差异（P > 0.05）。 GADA、IA-2A 或 IAA 经常出现在具有 DQA1*03-DQB1*0303 单倍型的 FDR 中。研究结果表明，一些特定的 HLA-DQA1/-DQB1 基因型和单倍型不仅导致对 T1D 的易感性，而且还与中国汉族人群中胰岛自身抗体的存在有关。
The objective of this study was to explore the relationship between islet autoantibodies of glutamic acid decarboxylase (GADA), islet antigen-2A (IA-2A), insulin autoantibody (IAA), and human leukocyte antigen (HLA)-DQ genotypes in type 1 diabetes (T1D) patients and their first-degree relatives (FDRs). Cross-sectional and case-control study. Four hundred and ninety-five T1D patients, 419 FDRs, and 376 control subjects in Han Chinese populations were recruited and tested for GADA and IA-2A, while 71 cases, all FDRs and 300 controls were tested for IAA. The 338 T1D patients (including 187 antibody-positive and 151 antibody-negative patients), 173 FDRs and 278 controls were genotyped for HLA-DQ with polymerase chain reaction sequencing-based method. Compared with the control, the frequency of DQA1*03-DQB1*0303, DQA1*05-DQB1*0201, and DQA1*03-DQB1*0401 haplotypes was higher (P < 0.05-0.01) but DQA1*0102-DQB1*0602 haplotype was lower (P < 0.01) in T1D patients. DQA1*03 allele was less in the FDRs than in their probands (P < 0.05). GADA was more prevalent in T1D patients carrying DQA1*05-DQB1*0201 or DQA1*03-DQB1*0401 haplotype (55.8% vs 41.0%, 65.5% vs 40.3%, P < 0.05-0.01), whereas IA-2A presented more in the patients carrying DQA1*03-DQB1*0303 haplotype (27.0% vs 7.9%, P < 0.05-0.01), both GADA and IA-2A showed frequently in the patients with DQA1*03-DQB1*0303/DQA1*05-DQB1*0201 haplotypes (34.5% vs 9.7%, P < 0.01). GADA positivity was lower in the patients with DQA1*0102-DQB1*0602 haplotype (16.7% vs 45.9%, P < 0.05). The frequency of IAA was not different between patients with and without susceptible DQ haplotypes (P > 0.05). GADA, IA-2A or IAA presented frequently in FDRs with DQA1*03-DQB1*0303 haplotype. The findings in the study indicate that some of specific HLA-DQA1/-DQB1 genotypes and haplotypes not only confer susceptibility to T1D but also are associated with the presence of the islet autoantibodies in the Han Chinese population.