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新诊断 1 型糖尿病患儿中 ZnT8Ab、SLC30A8 基因与疾病进展的关系。

Relationship between ZnT8Ab, the SLC30A8 gene and disease progression in children with newly diagnosed type 1 diabetes.

机构信息

Department of Paediatrics, Glostrup University Hospital, Glostrup, Denmark.

出版信息

Autoimmunity. 2011 Dec;44(8):616-23. doi: 10.3109/08916934.2011.576724. Epub 2011 May 23.

DOI:10.3109/08916934.2011.576724
PMID:21604969
Abstract

Autoantibodies against the newly established autoantigen in type 1 diabetes, zinc transporter 8, ZnT8, are presented as two types, ZnT8RAb and ZnT8WAb. The rs13266634 variant of the SLC30A8 gene has recently been found to determine the type of ZnT8Ab. The aim of this study was to explore the impact of this genetic variant and the ZnT8Ab on the residual beta-cell function during disease progression the first year after disease diagnosis in children with newly diagnosed type 1 diabetes. This cohort consists of 257 children aged < 16 years, all patients were newly diagnosed with type 1 diabetes. A Boost-test was carried out at 1, 6, and 12 months to characterize the residual beta-cell function. Carriers of the CC and CT genotype groups of the rs13266634 SNP of the SLC30A8 gene had higher stimulated C-peptide levels the first year after onset compared with those of the TT genotype group (29%, p = 0.034). CC genotype carriers were highly associated with the presence of ZnT8RAb subtype during disease progression (compared with TT, p < 0.0001). On the other hand, the TT genotype was associated with the presence of ZnT8WAb subtype during disease progression (compared with CC, p < 0.0001). The C allele of the SLC30A8 gene is associated with preserved beta-cell function in type 1 diabetes patients. The genetic determination of the rs13266634 variant on the ZnT8Ab specificity is sustained the first 12 months after the diagnosis of type 1 diabetes in a pediatric cohort.

摘要

自身抗体针对新建立的 1 型糖尿病自身抗原,锌转运体 8,ZnT8,表现为两种类型,ZnT8RAb 和 ZnT8WAb。SLC30A8 基因的 rs13266634 变体最近被发现决定 ZnT8Ab 的类型。本研究旨在探讨这种遗传变异体和 ZnT8Ab 对新诊断的 1 型糖尿病儿童发病后第一年疾病进展过程中残留β细胞功能的影响。该队列由 257 名年龄<16 岁的儿童组成,所有患者均被新诊断为 1 型糖尿病。在 1、6 和 12 个月进行 Boost 测试以评估残留的β细胞功能。SLC30A8 基因 rs13266634 SNP 的 CC 和 CT 基因型组的携带者在发病后第一年的刺激 C 肽水平高于 TT 基因型组(29%,p=0.034)。CC 基因型携带者在疾病进展过程中与 ZnT8RAb 亚型的存在高度相关(与 TT 相比,p<0.0001)。另一方面,TT 基因型与疾病进展过程中 ZnT8WAb 亚型的存在相关(与 CC 相比,p<0.0001)。SLC30A8 基因的 C 等位基因与 1 型糖尿病患者的β细胞功能保存有关。在儿科队列中,rs13266634 变异的遗传决定在 1 型糖尿病诊断后 12 个月内持续存在 ZnT8Ab 特异性。

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