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The aim of this study was to perform a meta-analysis of eligible studies and to derive a precise estimate of the association between interleukin 10 (IL10) polymorphisms and susceptibility to autoimmune thyroid disease (AITD). Meta-analyses were conducted on the associations between AITD and the -1082 G/A (rs1800896), -819 C/T (rs1800871) and -592 C/A (rs1800872) polymorphisms in IL10, and the haplotype of these polymorphisms and AITD. A total of 2903 AITD patients and 3060 controls in 10 eligible studies were included in the meta-analysis. This meta-analysis showed significant associations between IL10 at the -1082 G allele and overall AITD (OR: 1.44, 95% CI 1.13-1.82, P = 0.003), but no association between the IL10 -592 C allele and the -819 C allele and AITD. Subgroup studies demonstrated significant associations between the -1082 G allele and susceptibility to Graves' disease. Ethnicity-specific meta-analysis revealed significant associations between the -1082 G allele and AITD susceptibility in Asian populations; however, in Middle Eastern populations, no association was evident. Meta-analysis of the IL10 haplotype revealed an association between the ATA haplotype and AITD (OR: 1.17, 95% CI 1.00-1.36, P = 0.04). Meta-analysis demonstrates that the IL10 polymorphisms are associated with susceptibility to AITD., (© 2016 The Foundation for the Scandinavian Journal of Immunology.)

Autoimmune thyroid disease (AITD), including Graves disease (GD) and Hashimoto disease (HD), is an organ-specific autoimmune disease with a strong genetic component. Although the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) polymorphism has been reported to be associated with AITD in adults, few studies have focused on children. The aim of our study was to investigate whether the CTLA4 polymorphisms, including -318C/T (rs5742909), +49A/G (rs231775), and CT60 (rs3087243), were associated with GD and HD in Han Chinese adults and children. We studied 289 adult GD, 265 pediatric GD, 229 pediatric HD patients, and 1058 healthy controls and then compared genotype, allele, carrier, and haplotype frequencies between patients and controls. We found that CTLA4 SNPs +49A/G and CT60 were associated with GD in adults and children. Allele G of +49A/G was significantly associated with GD in adults (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.21-1.84; corrected P value [Pc] < 0.001) and children (OR, 1.42; 95% CI, 1.15-1.77; Pc = 0.002). Allele G of CT60 also significantly increased risk of GD in adults (OR, 1.63; 95% CI, 1.27-2.09; Pc < 0.001) and GD in children (OR, 1.58; 95% CI, 1.22-2.04; Pc < 0.001). Significant linkage disequilibrium was found between +49A/G and CT60 in GD and control subjects (D' = 0.92). Our results showed that CTLA4 was associated with both GD and HD and played an equivalent role in both adult and pediatric GD in Han Chinese population.

This study was to investigate whether the common polymorphisms of CD40 and CTLA4 genes confer susceptibility to AITD in the Chinese population. A set of unrelated subjects including 303 GD patients, 208 HT patients, and 215 matched healthy controls were recruited. SNPs were genotyped by the method of PCR-RFLP. (1) As for CD40 C/T(-1) SNP, only a significant difference was found in allele frequencies between GD and control groups (P = 0.033). (2) On the part of CTLA-4 A/G(49) SNP, significant differences were found in genotype and allele frequencies between GD and control groups (P = 7.0 × 10(-5) and P = 0.002, respectively), and similar results were found between HT and control groups (P = 0.015 and P = 0.003, respectively). (3) The logistic regression analysis showed there was no interaction between CD40 and CTLA4 genotypes (P = 0.262). These results indicate that both CTLA-4 A/G(49) and CD40 C/T(-1) SNPs are associated with genetic susceptibility of GD, and CTLA-4 A/G(49) is also associated with HT.

Background: Previous studies on relatively small populations of patients with primary Sjögren's syndrome (pSS) suggested an association between pSS and Hashimoto's thyroiditis (HT). As some findings in the literature regarding the relationship between pSS and thyroid disease are contradictory, and there is little information on the sequence of pSS and HT, we conducted a study with a population of patients with pSS that was about three times larger than previously studied populations. Our objective was to determine the prevalence of HT and Graves' disease (GD) in patients with pSS and to assess the sequence of pSS and autoimmune thyroid diseases., Methods: A total of 479 patients with pSS were retrospectively studied. Thyroid ultrasound and scintigraphy were performed, and serum thyrotropin, free triiodothyronine, free thyroxine, antithyroid peroxidase antibody (TPOAb), and anti-thyroglobulin autoantibody (TgAb) measurements were carried out. Solitary thyroid nodules were investigated by fine-needle aspiration biopsy., Results: Thyroid dysfunction was found in 95 patients (21.25%). Thirty of these patients had HT and 18 had GD. HT predated pSS in eight patients, developed at approximately the same time in seven patients, and followed pSS in 15 patients. Almost all (90%) patients with HT had persistently elevated serum TgAb or TPOAb titers., Conclusions: An association between HT and pSS was found based on the fact that the frequency of HT was greater among pSS patients (6.26%) than in the general population (1-2%). In contrast, no association between GD and pSS was found. We noted that both HT and GD can appear either before or after the onset of pSS. Since most cases of pSS predate the appearance of autoimmune thyroid diseases it is important to determine if pSS is a predisposing factor for the development of autoimmune thyroiditis.

Graves' disease (GD) and Hashimoto's thyroiditis (HT) are both common autoimmune diseases of the thyroid gland (AITD). The IL-4 is involved in both humoral and cellular immunity. The aim of this study was to test whether the IL-4 gene could be used as a genetic marker to predict the development of AITD amongst the Chinese population of Taiwan. For this study, a normal control group of 105 healthy subjects and two experimental groups featuring individuals afflicted with either GD (104 patients) or HT (109 patients) were examined. Polymerase chain reaction (PCR) was used to analyze the variable number of tandem repeats (VNTRs) polymorphism for the IL-4 gene intron 3 and PCR-based restriction analysis using endonuclease BsmFI was undertaken for the same gene at the promoter -590 position. We found no significant difference in the frequencies of presence of genotype and allelic variants for the IL-4 gene at both the intron 3 and the promoter regions between the normal control group and each of the two patient groups. These findings suggest that the IL-4 gene polymorphisms that arise at either intron 3 or promoter -590 positions are not suitable genetic markers for AITD among Taiwanese Chinese.