Autoimmune thyroid diseases (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT) are complex genetic diseases. Th2 cytokines act on the development of AITD. This study was conducted on Tunisian patients with AITD to investigate the association of Th2 cytokine gene polymorphisms and haplotype combination with GD or HT risk. A total of 156 controls, 160 patients with HT and 88 patients with GD were genotyped for IL‐4 rs2243250, IL‐5 rs2069812, IL‐6 rs1800796 and IL‐13 rs1800925 polymorphisms by PCR‐RFLP. The AITD risk was assessed by a logistic regression analysis using the SNP stats statistical program. False‐positive report probability (FPRP) was estimated to evaluate significant findings. IL‐13 rs1800925 was associated with GD, after adjustment for age and gender, in codominant, dominant and allele genetic models (p = .0072; p = .0018; p = .012, respectively). Significant association of the IL‐6 rs1800796C/G genotype with GD was also detected (p = .025). Furthermore, increased risk of HT was still found for IL‐13 rs1800925T allele (p = .039, OR = 1.39) and for IL‐4 rs2243250T/T genotype both in codominant (p = .033, OR = 2.59) and recessive (p = .011, OR = 2.73) models after adjustment for age and gender. Interestingly, haplotype analysis performed on the IL‐4, IL‐5 and IL‐13 genes revealed a high risk of HT with CTT haplotype (p = .008, OR = 2.12). However, the CCT haplotype is a protective factor (OR = 0.36). Patients carrying the CT haplotype with only one minor allele had a moderate risk of HT (OR = 1.56). The FPRP analysis showed that the association of IL‐13 rs1800925 polymorphism with GD and HT and the association of CTT haplotype with HT were noteworthy. In conclusion, the IL‐4, IL‐5, IL‐6 and IL‐13 polymorphism may play a role in susceptibility to GD and HT in the Tunisian population. Furthermore, gene–gene interaction between the IL‐4, IL‐5 and IL‐13 significantly increases the risk of AITD. Further studies with larger numbers of individuals are needed to confirm the results.

中文翻译：

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突尼斯人群细胞因子Th2基因多态性与自身免疫性甲状腺疾病的相关性

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) 是复杂的遗传疾病。Th2细胞因子作用于AITD的发展。这项研究是针对突尼斯 AITD 患者进行的，以调查 Th2 细胞因子基因多态性和单倍型组合与 GD 或 HT 风险的关联。共有 156 名对照者、160 名 HT 患者和 88 名 GD 患者通过 PCR-RF LP 进行了 IL-4 rs2243250、IL-5 rs2069812、IL-6 rs1800796 和 IL-13 rs1800925 多态性的基因分型。AITD 风险通过逻辑回归分析使用 SNP 统计程序进行评估。估计假阳性报告概率 (FPRP) 以评估重要发现。在调整年龄和性别后，在共显性、显性和等位基因遗传模型中，IL-13 rs1800925 与 GD 相关（p = . 0072; p = .0018；p = .012，分别）。还检测到 IL-6 rs1800796C/G 基因型与 GD 的显着关联（p = .025）。此外，IL-13 rs1800925T 等位基因（p = .039，OR = 1.39）和 IL-4 rs2243250T/T 基因型的 HT 风险仍然增加，无论是共显性（p = .033，OR = 2.59）还是隐性（ p = .011, OR = 2.73) 年龄和性别调整后的模型。有趣的是，对 IL-4、IL-5 和 IL-13 基因进行的单倍型分析显示，CTT 单倍型的 HT 风险很高（p = .008，OR = 2.12）。然而，CCT 单倍型是一个保护因素（OR = 0.36）。携带只有一个次要等位基因的 CT 单倍型的患者患 HT 的风险中等（OR = 1.56）。FPRP分析表明IL-13 rs1800925多态性与GD和HT的关联以及CTT单倍型与HT的关联值得注意。总之，IL-4、IL-5、IL-6 和 IL-13 多态性可能在突尼斯人群对 GD 和 HT 的易感性中起作用。此外，IL-4、IL-5 和 IL-13 之间的基因-基因相互作用显着增加了 AITD 的风险。需要对更多个体进行进一步研究以确认结果。