Discordant association of islet autoantibodies with high-risk HLA genes in Chinese type 1 diabetes
Discordant association of islet autoantibodies with high-risk HLA genes in Chinese type 1 diabetes
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中国 1 型糖尿病中胰岛自身抗体与高危 HLA 基因的不一致关联
DOI：
10.1002/dmrr.1270
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发表时间：
2011-11-01
影响因子：
8
通讯作者：
Yang, Tao
中科院分区：
文献类型：
--
作者：
Gu, Yong;Zhang, Mei;Yang, Tao
目的探讨1型糖尿病（T1 D）患者胰岛自身抗体、人类白细胞抗原（HLA）-A和DRB 1基因型与T1 D发病的关系。采用聚合酶链反应-序列寡核苷酸探针法检测HLA-A和DRB 1基因多态性。结果A*2402、DRB 1 *0301、DRB 1 *0405、DRB 1 * 0901等位基因和A*1101-DRB 1 * 0901、A* 110 A*2402-DRB 1 *0405和A*2402-DRB 1 *0901单倍型与T1 D相关（均p < 0.05）。DRB 1 0 90 1和A 110 1-DRB 1 0 90 1携带者的ZnT 8A、IA 2 A和GADA阳性率均显著高于非DRB 1 0 90 1和A 2 4 0 2-DRB 1 0 90 1携带者（P <0.0 5）。HLA-DRB 1 *0901是T1 D患者抗体阳性的独立危险因素。除HLA高危基因和胰岛自身抗体外，高体重指数也与胰岛功能丧失有关（p < 0.05）。结论自身抗体与HLA高危基因的不一致性可能反映了不同自身抗体的免疫学机制。超重引起的代谢负荷可加速β细胞凋亡。版权所有（C）2011约翰威利父子有限公司
Background To reveal the aetiology of diabetes, the relationships between the islet autoantibodies, human leukocyte antigen (HLA)-A and DRB1 genotypes in the Chinese patients with type l diabetes (T1D) were investigated in our study.Methods In the cross-sectional and case-control study, peripheral blood samples were collected from 600 T1D patients and 102 healthy controls. The genetic polymorphisms of HLA-A and DRB1 are examined with polymerase chain reaction-sequence oligonucleotide probe method. The zinc transporter 8 antibody (ZnT8A), glutamic acid decarboxylase antibody (GADA) and protein-tyrosine-phosphatase-2 autoantibody (IA2A) were detected by radioligand assay.Results The A*2402, DRB1*0301, DRB1*0405 and DRB1*0901 alleles, and A*1101-DRB1*0901, A*2402-DRB1*0405 and A*2402-DRB1*0901 haplotypes were associated with T1D (all p < 0.05). The positive rates of ZnT8A in patients carried DRB1*0901, IA2A in patients carried DRB1*0405 and A*1101-DRB1*0901 and GADA in patients carried DRB1*0901 and A*2402-DRB1*0901 were significantly higher than those not carried (p < 0.05). HLA-DRB1*0901 was the independent risk factor of positive antibody in T1D patients. In addition, higher body mass index is also related with the loss of islet function besides high-risk HLA gene and islet autoantibody (p < 0.05).Conclusions The discordant association of autoantibodies with high-risk HLA gene may indicate the different immunology mechanisms of those autoantibodies. And metabolic burden resulting from overweight may accelerate apoptosis of beta cells. Copyright (C) 2011 John Wiley & Sons, Ltd.