Gene polymorphisms of pro-inflammatory cytokines may affect the risk of Graves' disease: a meta-analysis

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ORIGINAL ARTICLE

Gene polymorphisms of pro‑inflammatory cytokines may affect the risk of Graves’ disease: a meta‑analysis P. Zhu1 · X. Wu1 · J. Zhou1 · K. Wu2 · Y. Lu3 Received: 22 April 2020 / Accepted: 15 May 2020 © Italian Society of Endocrinology (SIE) 2020

Abstract Purpose  Gene polymorphisms of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) may influence the risk of Graves’ disease, but the results of so far published studies remain inconclusive. Therefore, the authors conducted this meta-analysis to assess relationships between TNF-α/IL-1/IL-6 polymorphisms and the risk of Graves’ disease by pooling the findings of all relevant studies. Methods  A comprehensive literature searching of Pubmed, Embase, Web of Science and CNKI was conducted by the authors, and twenty-eight studies were found to be eligible for pooled analyses. Results  The pooled meta-analyses results showed that genotypic frequencies of TNF-α rs1800629, IL-1A rs1800587, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms among patients with Graves’ disease and control subjects differed significantly. Moreover, we found that genotypic frequencies of TNF-α rs1800629 and IL-6 rs1800795 polymorphisms among patients with Graves’ disease and control subjects in Caucasians differed significantly, and genotypic frequencies of IL-1A rs1800587, IL-1B rs16944, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms among patients with Graves’ disease and control subjects in Asians also differed significantly. Nevertheless, we did not detect such genotypic frequencies differences for TNF-α rs361525 and IL-1B rs1143627 polymorphisms. Conclusions  This meta-analysis suggests that TNF-α rs1800629, IL-1A rs1800587, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms may influence the risk of Graves’ disease in overall population. Moreover, TNF-α rs1800629 and IL-6 rs1800795 polymorphisms may influence the risk of Graves’ disease in Caucasians, while IL-1A rs1800587, IL-1B rs16944, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms may influence the risk of Graves’ disease in Asians. Keywords  Graves’ disease · Tumor necrosis factor-α (TNF-α) · Interleukin-1 (IL-1) · Interleukin-6 (IL-6) · Gene polymorphisms

Introduction

Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s4061​8-020-01300​-x) contains supplementary material, which is available to authorized users. * Y. Lu [email protected] 1



Department of Endocrinology, Huaian Hospital of Huaian District, Huaian 223200, China

2



Department of Clinical Medicine, Yangzhou University Medical College, Yangzhou 225009, China

3

Department of Endocrinology, Xiamen Haicang Hospital, Xiamen 361026, China



Graves’ disease is characterized by a hyperthyroid status due to excessive production of thyroid hormones [1]. It is a quite common endocrine disorder, which affects approximately 0.5–1% of general population, and around 80% of hyperthyroidism is found to be caused by the Graves’ disease [2]. The exact pathoge