Abstract
Objectives: The signal transducer and activator of transcription 4 (STAT4) gene encodes an important transcription factor that transmits signals induced by several cytokines associated with autoimmune diseases and has been identified as a susceptibility gene for numerous autoimmune disorders. The association between STAT4 rs7574865 polymorphism and the susceptibility of autoimmune thyroid disease (AITD) has been investigated in previous case-control studies. However, the investigation results were inconsistent. Hence, a meta-analysis was performed to draw a more reliable conclusion about it.Methods: All relevant studies were searched in Embase, PubMed, Web of Science, and China National Knowledge Infrastructure, till August 20, 2018. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the association.Results: A total of five independent case-control studies with 1707 AITD patients and 2316 controls were included in the present meta-analysis. The overall pooled analysis indicated that STAT4 rs7574865 polymorphism was significantly associated with AITD susceptibility [TT vs. GG: OR = 1.63, 95%CI = 1.24–2.15, PZ = 0.0005; TT vs. (TG+GG): OR = 1.55, 95%CI = 1.26–1.91, PZ < 0.0001]. However, the subgroup analysis showed a significant association of STAT4 rs7574865 polymorphism with AITD susceptibility in Asian population, but not in African population. STAT4 rs7574865 polymorphism was significantly associated both with Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) susceptibility.Conclusion: This meta-analysis showed a significant association between STAT4 rs7574865 polymorphism and AITD susceptibility. However, further studies with larger sample sizes and other ethnicities are still required to confirm the findings.
Highlights
Autoimmune thyroid disease (AITD) affects approximately 5% of the general population (Tunbridge et al, 1977; Hollowell et al, 2002)
Eligible studies were chosen by two authors independently (XR Gao and JG Wang) according to the following inclusion criteria: (i) case-control studies that assessed the relationship between Signal transducer and activator of transcription 4 (STAT4) rs7574865 polymorphism and AITD susceptibility; (ii) studies that contained the distribution of allelic or genotypic frequencies of STAT4 rs7574865 polymorphism in all participants; (iii) studies that scored more than six stars based on the Newcastle-Ottawa Scale (NOS), which was adopted to assess the methodological quality of each candidate study (Stang, 2010)
Yan et al (2014) investigated the role of the STAT4 rs7574865 polymorphism in AITD susceptibility by a Chinese case-control study (1044 patients affected with AITD and 903 healthy controls), and the results indicated that the frequencies of STAT4 rs7574865 genotypes in Graves’ disease (GD) patients were significantly different from that in the controls, and the T allele frequency of GD patients was significantly higher than the controls
Summary
Autoimmune thyroid disease (AITD) affects approximately 5% of the general population (Tunbridge et al, 1977; Hollowell et al, 2002). During the last several decades, great progress has been made in the study of AITD risk factors. Epidemiological studies have pointed out several environmental factors triggering AITD, such as viral infections, drugs, irradiation and iodine intake, which probably involve interference with thyroid function, immune stimulation, direct toxic effects on thyrocytes, or other immunomodulatory effects (Orgiazzi, 2012; Antonelli et al, 2015). Increasing evidences have suggested that individual genetic factors play an important role in the risk of AITD (Ban et al, 2005; Durães et al, 2014; Lin et al, 2016). The exploration of genetic factors associated with AITD risk will contribute to risk assessment and prevention of disease
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