Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Diabetes Metab Res Rev. 2011 Nov;27(8):899-905. doi: 10.1002/dmrr.1270.
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.
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.
The A2402, DRB10301, DRB10405 and DRB10901 alleles, and A1101-DRB10901, A2402-DRB10405 and A2402-DRB10901 haplotypes were associated with T1D (all p<0.05). The positive rates of ZnT8A in patients carried DRB10901, IA2A in patients carried DRB10405 and A1101-DRB10901 and GADA in patients carried DRB10901 and A2402-DRB10901 were significantly higher than those not carried (p<0.05). HLA-DRB10901 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).
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.
为了揭示糖尿病的病因，我们研究了中国 1 型糖尿病（T1D）患者胰岛自身抗体与人类白细胞抗原（HLA）-A 和 DRB1 基因型之间的关系。
在这项横断面和病例对照研究中，采集了 600 例 T1D 患者和 102 例健康对照者的外周血样本。采用聚合酶链反应-序列寡核苷酸探针法检测 HLA-A 和 DRB1 基因多态性。采用放射配体法检测锌转运体 8 抗体（ZnT8A）、谷氨酸脱羧酶抗体（GADA）和蛋白酪氨酸磷酸酶-2 自身抗体（IA2A）。
A2402、DRB10301、DRB10405 和 DRB10901 等位基因以及 A1101-DRB10901、A2402-DRB10405 和 A2402-DRB10901 单倍型与 T1D 相关（均 P<0.05）。携带 DRB10901 的患者中 ZnT8A 的阳性率、携带 DRB10405 的患者中 IA2A 的阳性率、携带 A1101-DRB10901 的患者中 GADA 的阳性率以及携带 DRB10901 和 A2402-DRB10901 的患者中 GADA 的阳性率均显著高于未携带的患者（均 P<0.05）。HLA-DRB10901 是 T1D 患者抗体阳性的独立危险因素。此外，除了高危 HLA 基因和胰岛自身抗体外，超重导致的更高的体重指数也与胰岛功能丧失有关（P<0.05）。
自身抗体与高危 HLA 基因之间的不一致关联可能表明这些自身抗体具有不同的免疫学机制。超重导致的代谢负担可能加速β细胞的凋亡。
