当前位置: X-MOL 学术Cent. Eur. J. Immunol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
STAT4 sequence variant and elevated gene expression are associated with type 1 diabetes in Polish children.
Central European Journal of Immunology ( IF 1.5 ) Pub Date : 2020-01-01 , DOI: 10.5114/ceji.2019.92492
Marta Fichna 1 , Magdalena Żurawek 2 , Klaudia Bogusz-Górna 3 , Piotr P Małecki 4 , Elżbieta Niechciał 3 , Anna Sidoruk 5 , Katarzyna Furman 6 , Piotr Fichna 3
Affiliation  

INTRODUCTION Type 1 diabetes (T1D) is caused by the autoimmune destruction of pancreatic β cells, resulting from coincident genetic predisposition and some environmental triggers. Signal transducer and activator of transcription 4 (STAT4) gene encodes a transcription factor, which promotes Th1 cell differentiation, interferon γ production, and development of Th17 cells. Polymorphisms of STAT4 are associated with several autoimmune conditions, while studies in T1D provided inconsistent results. This analysis was designed to investigate the association of STAT4 rs7574865 with T1D in Polish children and to assess STAT4 expression in newly diagnosed subjects. MATERIAL AND METHODS Rs7574865 was genotyped in 656 T1D children and 782 healthy individuals. STAT4 mRNA expression was analyzed in peripheral blood mononuclear cells (PBMCs) from 29 children with T1D and 27 age-matched controls. β-cell and thyroid-specific serum autoantibodies were assessed with radioimmunoassays. RESULTS The distribution of rs7574865 genotypes and alleles demonstrated significant difference (p = 0.002, p < 0.001, respectively) between patients vs. controls. Carriers of the minor T allele presented earlier T1D onset (p = 0.017). No differences were found in γ-cell autoantibody in genotype-stratified patients (p > 0.050), while anti-thyroid antibodies were more frequent in carriers of the minor allele(p = 0.039 for anti-thyroperoxidase, p = 0.007 for anti-thyroglobulin antibodies, respectively). STAT4 was overexpressed in PBMCs from T1D patients (p = 0.008), especially subjects with two/three circulating β-cell antibodies (p < 0.001). CONCLUSIONS The study confirms an association of STAT4 rs7574865 with T1D in Polish patients, and provides an evidence for its relationship with an earlier disease onset and concomitant thyroid autoimmunity. STAT4 expression appears elevated in T1D, especially with more severe reaction against β-cell antigens.

中文翻译:

STAT4 序列变异和基因表达升高与波兰儿童的 1 型糖尿病有关。

引言 1 型糖尿病 (T1D) 是由胰腺 β 细胞的自身免疫性破坏引起的,由同时发生的遗传易感性和一些环境诱因引起。信号转导和转录激活因子 4 (STAT4) 基因编码一种转录因子,可促进 Th1 细胞分化、干扰素 γ 的产生和 Th17 细胞的发育。STAT4 的多态性与几种自身免疫性疾病相关,而 T1D 的研究提供了不一致的结果。该分析旨在调查 STAT4 rs7574865 与波兰儿童 T1D 的关联,并评估新诊断受试者中的 STAT4 表达。材料和方法 Rs7574865 在 656 名 T1D 儿童和 782 名健康个体中进行基因分型。在来自 29 名 T1D 患儿和 27 名年龄匹配对照的外周血单个核细胞 (PBMC) 中分析了 STAT4 mRNA 表达。用放射免疫测定法评估β细胞和甲状腺特异性血清自身抗体。结果 rs7574865 基因型和等位基因的分布在患者与对照组之间表现出显着差异(分别为 p = 0.002,p < 0.001)。次要 T 等位基因的携带者出现较早的 T1D 发病 (p = 0.017)。基因型分层患者的 γ 细胞自身抗体无差异(p > 0.050),而抗甲状腺抗体在次要等位基因携带者中更常见(抗甲状腺过氧化物酶 p = 0.039,抗甲状腺球蛋白 p = 0.007抗体,分别)。STAT4 在 T1D 患者的 PBMC 中过表达(p = 0.008),尤其是具有两个/三个循环 β 细胞抗体的受试者(p < 0.001)。结论 该研究证实了波兰患者中 STAT4 rs7574865 与 T1D 的关联,并为其与早期疾病发作和伴随的甲状腺自身免疫的关系提供了证据。STAT4 表达在 T1D 中似乎升高,尤其是对 β 细胞抗原的反应更严重。
更新日期:2020-01-01
down
wechat
bug