Polymorphisms in the TNFA and IL6 Genes Represent Risk Factors for Autoimmune Thyroid Disease

Abstract

BackgroundAutoimmune thyroid disease (AITD) comprises diseases including Hashimoto's thyroiditis and Graves' disease, both characterized by reactivity to autoantigens causing, respectively, inflammatory destruction and autoimmune stimulation of the thyroid-stimulating hormone receptor. AITD is the most common thyroid disease and the leading form of autoimmune disease in women. Cytokines are key regulators of the immune and inflammatory responses; therefore, genetic variants at cytokine-encoding genes are potential risk factors for AITD.MethodsPolymorphisms in the IL6-174 G/C (rs1800795), TNFA-308 G/A (rs1800629), IL1B-511 C/T (rs16944), and IFNGR1-56 T/C (rs2234711) genes were assessed in a case-control study comprising 420 Hashimoto's thyroiditis patients, 111 Graves' disease patients and 735 unrelated controls from Portugal. Genetic variants were discriminated by real-time PCR using TaqMan SNP genotyping assays.ResultsA significant association was found between the allele A in TNFA-308 G/A and Hashimoto's thyroiditis, both in the dominant (OR = 1.82, CI = 1.37–2.43, p-value = 4.4×10−5) and log-additive (OR = 1.64, CI = 1.28–2.10, p-value = 8.2×10−5) models. The allele C in IL6-174 G/C is also associated with Hashimoto's thyroiditis, however, only retained significance after multiple testing correction in the log-additive model (OR = 1.28, CI = 1.06–1.54, p-value = 8.9×10−3). The group with Graves' disease also registered a higher frequency of the allele A in TNFA-308 G/A compared with controls both in the dominant (OR = 1.85, CI = 1.19–2.87, p-value = 7.0×10−3) and log-additive (OR = 1.69, CI = 1.17–2.44, p-value = 6.6×10−3) models. The risk for Hashimoto's thyroiditis and Graves' disease increases with the number of risk alleles (OR for two risk alleles is, respectively, 2.27 and 2.59).ConclusionsThis study reports significant associations of genetic variants in TNFA and IL6 with the risk for AITD, highlighting the relevance of polymorphisms in inflammation-related genes in the etiopathogenesis of AITD.

Lower Serum 25-Hydroxyvitamin D Level is Associated With 3 Types of Autoimmune Thyroid Diseases

“…For example, vitamin D takes part in the regulation of cytokines, such as interleukin (IL)-1, IL-6, IL-17, TNF-α, and leptin, which has been found to play an important role in AITD. 1 – 4 , 35 – 37 Further research is required in this field. Would supplementation of vitamin D be beneficial to AITD patients, given that lower serum vitamin D level is associated with higher risk of this disease?…”

“…Autoimmune thyroid diseases (AITD) are the most common organ specific autoimmune disorder. 1 – 3 Graves’ disease (GD) and Hashimoto's thyroiditis (HT) are the 2 main clinical presentations of AITD and are both characterized by lymphocytic infiltration of the thyroid parenchyma. The clinical hallmarks of GD and HT are thyrotoxicosis and hypothyroidism, respectively.…”

Promoter Polymorphism (-174, G/C) of Interleukin-6 and Arterial Thromboembolic Events: A Meta-Analysis

“…In patients with type 2 diabetes, rs1800795 SNP of the IL-6 gene is significantly related to increased risk of cardiovascular disease [15]. In addition, rs1800795 SNP of the IL-6 gene is related with autoimmune diseases such as systemic lupus erythematosus [16], systemic sclerosis [17], and autoimmune thyroid disease [18]. …”

Possible role of IL-6 and TIE2 gene polymorphisms in predicting the initial high transport status in patients with peritoneal dialysis: an observational study

“…It has been shown that SNPs of IL-6 may influence the development of cardiovascular disease, 28 cancer, 29 30 fractures 31 and autoimmune diseases. [32][33][34] In contrast, there is less available research regarding TIE2 gene polymorphisms, except for a study on the relationship between rs638203/rs639225 and vascular malformations. 35 In this study, we investigated the effect of genetic polymorphisms of IL-6 and TIE2 on the baseline peritoneal transport property.…”