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

机译:ZnT8Ab,SLC30A8基因与初诊1型糖尿病儿童疾病进展的关系

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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.
机译:针对1型糖尿病中新建立的自身抗原的自身抗体,锌转运蛋白8,ZnT8,以ZnT8RAb和ZnT8WAb两种形式出现。最近发现SLC30A8基因的rs13266634变体可以确定ZnT8Ab的类型。这项研究的目的是探讨这种遗传变异和ZnT8Ab对新诊断的1型糖尿病儿童疾病诊断后第一年疾病进展期间残余β细胞功能的影响。该队列包括257名年龄<16岁的儿童,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测试以表征残留的β细胞功能。与TT基因型组相比,SLC30A8基因的rs13266634 SNP的CC和CT基因型组的携带者在发病后第一年的C肽刺激水平更高(29%,p = 0.034)。 CC基因型携带者与疾病进展过程中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型糖尿病患者中β细胞功能的维持有关。在小儿队列中诊断出1型糖尿病后的前12个月,对rs13266634变体的ZnT8Ab特异性进行了遗传测定。

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