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锌转运体 8 自身抗体在拉丁美洲 1 型糖尿病诊断中的重要性。

Importance of Zinc Transporter 8 Autoantibody in the Diagnosis of Type 1 Diabetes in Latin Americans.

机构信息

Laboratório de Carboidratos e Radioimunoensaio -LIM 18, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Av Dr. Arnaldo 455, 01246-903, São Paulo, Brazil.

Departamento de Genética e Biologia Evolutiva, Instituto de Biociências da Universidade de São Paulo. Rua do Matão, 277, 05422-970, São Paulo, São Paulo, Brazil.

出版信息

Sci Rep. 2017 Mar 16;7(1):207. doi: 10.1038/s41598-017-00307-4.

Abstract

UNLABELLED

There is a scarcity of data of zinc transporter-8 autoantibody (ZnT8A) on mixed populations such as Brazilian. Therefore, we evaluated the relevance of ZnT8A for type 1 diabetes (T1D) diagnosis and the role of ZnT8 coding gene (SLC30A8) in T1D predisposition. Patients with T1D (n = 629; diabetes duration = 11 (6-16) years) and 651 controls were genotyped for SLC30A8 rs16889462 and rs2466295 variants (BeadXpress platform). ZnT8 triple antibody was measured by ELISA; glutamic acid decarboxylase (GAD65A) and protein tyrosine phosphatase (IA-2A) autoantibodies by radioimmunoassay.

RESULTS

Znt8A was detected in 68.7% of recent-onset T1D patients and 48.9% of the entire patient cohort, similar to GAD65A (68.3% and 47.2%) and IA-2A (64.8% and 42.4%) positivities respectively. ZnT8A was the only antibody in 8.4% of patients. Znt8A and IA2A frequencies and titers were independent of gender and ethnicity, whereas GAD65A titers were greater in females. The diabetes duration-dependent decline in ZnT8A frequency was similar to GAD65A and IA-2A. The SLC30A8 rs2466293 AG + GG genotypes were associated with T1D risk in non-European descents (56.2% × 42.9%; p = 0.018), and the GG genotype with higher ZnT8A titers in recent-onset T1D: 834.5 IU/mL (711.3-2190.0) × 281 IU/mL (10.7-726.8); p = 0.027. Conclusion ZnT8A detection increases T1D diagnosis rate even in mixed populations. SLC30A8 rs2466293 was associated with T1D predisposition in non-European descents.

摘要

目的

评估锌转运蛋白 8 自身抗体(ZnT8A)在混合人群(如巴西人群)中对 1 型糖尿病(T1D)诊断的相关性,并研究锌转运蛋白编码基因(SLC30A8)在 T1D 易感性中的作用。

方法

对 629 例 T1D 患者(糖尿病病程 11(6-16)年)和 651 例对照进行 SLC30A8 rs16889462 和 rs2466295 变异(BeadXpress 平台)的基因分型。通过 ELISA 检测 ZnT8 三抗体;用放射免疫法检测谷氨酸脱羧酶(GAD65A)和蛋白酪氨酸磷酸酶(IA-2A)自身抗体。

结果

在新诊断的 T1D 患者中,ZnT8A 阳性率为 68.7%,在整个患者队列中为 48.9%,与 GAD65A(68.3%和 47.2%)和 IA-2A(64.8%和 42.4%)阳性率相似。在 8.4%的患者中只有 ZnT8A 抗体。ZnT8A 和 IA2A 的频率和滴度与性别和种族无关,而 GAD65A 滴度在女性中更高。ZnT8A 频率随糖尿病病程的下降与 GAD65A 和 IA-2A 相似。SLC30A8 rs2466293AG+GG 基因型与非欧洲血统的 T1D 风险相关(56.2%×42.9%;p=0.018),且 GG 基因型在新诊断的 T1D 患者中 ZnT8A 滴度更高:834.5IU/mL(711.3-2190.0)×281IU/mL(10.7-726.8);p=0.027。

结论

即使在混合人群中,检测 ZnT8A 也可提高 T1D 的诊断率。SLC30A8 rs2466293 与非欧洲血统的 T1D 易感性相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30bf/5428214/ea51e1049bf8/41598_2017_307_Fig1_HTML.jpg

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