白细胞介素2受体α链（IL2RA）、干扰素诱导解旋酶C结构域蛋白1（IFIH1）和细胞毒性T淋巴细胞相关蛋白4（CTLA-4）基因多态性与自身免疫性甲状腺疾病和1型糖尿病的遗传关联研究
Genetic Association Study of IL2RA, IFIH1, and CTLA-4 Polymorphisms With Autoimmune Thyroid Diseases and Type 1 Diabetes.
作者信息
Borysewicz-Sańczyk Hanna, Sawicka Beata, Wawrusiewicz-Kurylonek Natalia, Głowińska-Olszewska Barbara, Kadłubiska Anna, Gościk Joanna, Szadkowska Agnieszka, Łosiewicz Aleksandra, Młynarski Wojciech, Kretowski Adam, Bossowski Artur
机构信息
Department of Pediatrics, Endocrinology, Diabetology With Cardiology Division, Medical University of Bialystok, Bialystok, Poland.
Department of Endocrinology and Diabetes With Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
出版信息
Front Pediatr. 2020 Aug 21;8:481. doi: 10.3389/fped.2020.00481. eCollection 2020.
Autoimmune thyroid diseases (AITDs) which include Graves' disease (GD) and Hashimoto's thyroiditis (HT) as well as type 1 diabetes (T1D) are common autoimmune disorders in children. Many genes are involved in the modulation of the immune system and their polymorphisms might predispose to autoimmune diseases development. According to the literature genes encoding IL2RA (alpha subunit of Interleukin 2 receptor), IFIH1 (Interferon induced with helicase C domain 1) and CTLA-4 (cytotoxic T cell antigen 4) might be associated with autoimmune diseases pathogenesis. The aim of the study was to assess the association of chosen single nucleotide polymorphisms (SNPs) of IL2RA, IFIH1, and CTLA-4 genes in the group of Polish children with AITDs and in children with T1D. We analyzed single nucleotide polymorphisms (SNPs) in the IL2RA region (rs7093069), IFIH1 region (rs1990760) and CTLA-4 region (rs231775) in group of Polish children and adolescents with type 1 diabetes ( = 194) and autoimmune thyroid diseases (GD = 170, HT = 81) and healthy age and sex matched controls for comparison ( = 110). There were significant differences observed between T1D patients and control group in alleles of IL2RA (rs7093069 T > C) and CTLA-4 (rs231775 G > A). In addition, the study revealed T/T genotype at the IL2RA locus (rs7093069) and G/G genotype at the CTLA-4 locus (rs231775) to be statistically significant more frequent in children with T1D. Moreover, genotypes C/T and T/T at the IFIH1 locus (rs1990760) were significantly more frequent in patients with T1D than in controls. We observed no significant differences between AITD patients and a control group in analyzed SNPs. In conclusion, we detected that each allele T of rs7093069 SNP at the IL2RA locus and G allele of rs231775 SNP at the CTLA-4 locus as well as C/T and T/T genotypes of rs1990760 SNP at the IFIH1 locus are predisposing in terms of T1D development. Thereby, we confirmed that IL2RA, IFIH1, and CTLA-4 gene locus have a role in T1D susceptibility. The analysis of selected SNPs revealed no association with AITDs in a group of Polish children and adolescents.
自身免疫性甲状腺疾病（AITD）包括格雷夫斯病（GD）和桥本甲状腺炎（HT），以及1型糖尿病（T1D），是儿童常见的自身免疫性疾病。许多基因参与免疫系统的调节，其多态性可能易导致自身免疫性疾病的发生。根据文献，编码白细胞介素2受体α亚基（IL2RA）、含解旋酶C结构域的干扰素诱导蛋白1（IFIH1）和细胞毒性T细胞抗原4（CTLA - 4）的基因可能与自身免疫性疾病的发病机制有关。本研究的目的是评估波兰患AITD儿童组以及患T1D儿童中IL2RA、IFIH1和CTLA - 4基因所选单核苷酸多态性（SNP）的关联性。我们分析了波兰1型糖尿病儿童和青少年组（n = 194）、自身免疫性甲状腺疾病组（GD，n = 170；HT，n = 81）以及年龄和性别匹配的健康对照组（n = 110）中IL2RA区域（rs7093069）、IFIH1区域（rs1990760）和CTLA - 4区域（rs231775）的单核苷酸多态性（SNP）。在1型糖尿病患者和对照组之间，观察到IL2RA（rs7093069 T > C）和CTLA - 4（rs231775 G > A）等位基因存在显著差异。此外，研究发现1型糖尿病儿童中，IL2RA基因座（rs7093069）的T/T基因型和CTLA - 4基因座（rs231775）的G/G基因型在统计学上更为常见。而且，IFIH1基因座（rs1990760）的C/T和T/T基因型在1型糖尿病患者中比对照组显著更常见。我们在分析的SNP中未观察到AITD患者与对照组之间存在显著差异。总之，我们检测到IL2RA基因座rs7093069 SNP的每个T等位基因、CTLA - 4基因座rs231775 SNP的G等位基因以及IFIH1基因座rs1990760 SNP的C/T和T/T基因型在1型糖尿病发生方面具有易感性。由此，我们证实IL2RA、IFIH1和CTLA - 4基因座在1型糖尿病易感性中起作用。对所选SNP的分析显示，在波兰儿童和青少年组中与AITD无关联。
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