锌转运体8自身抗体对1型糖尿病诊断价值及其与HLA-A基因的关系
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镇江市社会发展科技支撑项目(SH2013052)


Diagnostic value of zinc transporter 8 autoantibody to type 1 diabetes mellitus and its relationship with HLA-A gene
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    摘要:

    目的:探讨锌转运体8自身抗体(zinc transporter 8 antibody, ZnT8A)在江苏地区1型糖尿病(type 1 diabetes mellitus, T1DM)诊断中的价值及ZnT8A与人类白细胞抗原(HLA)-A基因的关系。方法:横断面、病例对照研究,T1DM和正常对照组均采用免疫配体法检测胰岛自身抗体: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)和ZnT8A,PCR-SSO 方法进行HLA-A的分型。结果:①140例TIDM患者中65例ZnT8A阳性(阳性率46.4%),102例正常对照组中仅1例ZnT8A阳性(阳性率1.0%),差异有统计学意义(P<0.05);②联合检测GADA、IAA、IA-2A 3个传统抗体,至少1个抗体阳性率为70.7%(99/140);联合检测GADA、IAA、IA-2A和ZnT8A 4个抗体,至少1个抗体阳性率为86.4%(121/140)(P<0.05),ZnT8A在其他3个抗体阴性的患者中仍有15.7%的阳性率;③HLA-A*24在T1DM组较正常对照组明显升高(P<0.05,OR=1.654),A*33与正常对照组相比明显下降(P<0.05,OR=0.161);④HLA-A*02在ZnT8A阳性组明显高于ZnT8A阴性组(P<0.05,OR=0.318),在校正病程、发病年龄、体重指数(BMI)等可能影响因素后,差异无统计学意义。结论:ZnT8A 使T1DM患者自身抗体阳性率提高了15.7%,有助于提高T1DM的诊断;暂未发现HLA-A与ZnT8A的相关性。

    Abstract:

    Objective:To explore the diagnostic value of zinc transporter 8 autoantibody (ZnT8A) and the relationship between ZnT8A and human leukocyte antigen (HLA)-A genotype in the patients with type l diabetes mellitus (T1DM) in Jiangsu Province. Methods:A cross-sectional and case-control study was carried out. The glutamic acid decarboxylase antibody (GADA),protein tyrosine phosphatase-2 antibody (IA-2A),insulin antibody (IAA),and ZnT8A were detected by radioimmunity ligand assay and the HLA gene polymorphism of HLA-A was examined with PCR-SSO method in T1DM and healthy controls (HC). Results:①Among 140 T1DM cases,46.4% (65/140) had positive ZnT8A,while the positive rate in 102 healthy controls was 1.0% (1/102). The positive rate of ZnT8A was significantly higher in T1DM than that in HC (P<0.05). ②On the base of testing GADA,IAA and IA-2A,the positive rate of at least one antibody was 70.7%(99/140) and it increasd to 86.4% (121/140) when ZnT8A was further tested (P<0.05). ZnT8A in the other three antibody-negative patients still had a positive rate of 15.7%. ③HLA-A*24 in the T1DM group was significantly higher than that in the healthy control group (P<0.05,OR=1.654),while A*33 decreased significantly (P<0.05,OR=0.161) compared with the healthy control group. ④HLA-A*02 was significantly higher in the ZnT8A-positive group than in the ZnT8A-negative group (P<0.05,OR=0.318),but no significant difference was found after adjusting for the effect of course of disease,age of onset,and BMI. Conclusion:The positive rate of antibody increase by 15.7% in T1DM patients when ZnT8A is further tested. ZnT8A can improve the diagnostic sensitivity. No relationship between HLA-A and ZnT8A was found.

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钱 莉,杨 涛,陈小罗,王 丽,吴晨光,徐志刚.锌转运体8自身抗体对1型糖尿病诊断价值及其与HLA-A基因的关系[J].南京医科大学学报(自然科学版),2017,(10):1297-1301

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  • 收稿日期:2016-11-09
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  • 在线发布日期: 2017-11-06
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