Wen-juan Jiang

Association of single-nucleotide polymorphisms in the STAT3 gene with autoimmune thyroid disease in Chinese individuals.

The aim of this study was to investigate the association between signal transducer and activator of transcription 3 (STAT3) polymorphisms and autoimmune thyroid diseases and clinical features. We genotyped six single-nucleotide polymorphisms (SNPs) rs1053005, rs2293152, rs744166, rs17593222, rs2291281, and rs2291282 of STAT3 gene in 667 patients with autoimmune thyroid disease (417 Graves’ disease (GD) and 250 Hashimoto’s thyroiditis (HT)) and 301 healthy controls. The allele A from rs1053005 was significantly less frequent in both GD and HT patients (P = 0.0024, OR = 0.6958, 95%CI = 0.5508–0.8788; P = 0.0091, OR = 0.7013, 95%CI = 0.5397–0.9112, respectively). The AA genotype of rs1053005 was less in GD and HT patients too (P = 0.0025,OR = 0.6278, 95%CI = 0.466–0.847) and (P = 0.0036,OR = 0.601, 95%CI = 0.428–0.843). The allele G from rs17593222 increased the susceptibility to the ophthalmopathy development both in autoimmune thyroid disease (AITD) and GD patients (P = 0.0007, OR = 3.980, 95%CI = 1.871–8.464; P = 0.0081, OR = 3.378, 95%CI = 1.441–7.919, respectively). The allele A and AA genotype of SNP rs1053005 may protect individuals from the susceptibility to AITD and their frequency decreased in AITD patients. In addition, the allele G of rs17593222 may increase the ophthalmopathy risk in AITD patients. Our findings suggest the existence of association between STAT3 gene and AITD, thus adding STAT3 gene to the list of the predisposing genes to AITD.

Association between STAT4 Gene Polymorphisms and Autoimmune Thyroid Diseases in a Chinese Population

The STAT4 gene encodes a transcriptional factor that transmits signals induced by several key cytokines which play important roles in the development of autoimmune diseases. The aim of this study was to explore the association of STAT4 polymorphism with Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). A total of 1048 autoimmune thyroid diseases (AITDs) patients (693 with GD and 355 with HT) and 909 age- and gender-matched controls were examined. STAT4 polymorphisms (rs7574865/rs10181656/rs7572482) were genotyped by multiplex polymerase chain reaction (PCR) and ligase detection reaction (LDR). The results indicated that the frequencies of rs7574865 genotypes in patients with GD differed significantly from the controls (p = 0.028), the T allele frequency of GD patients was also significantly higher than the controls (p = 0.020). The genotypes of rs10181656 differed significantly in GD patients from controls (p = 0.012); G allele frequencies were significantly higher in AITD patients than the controls (p = 0.014 and 0.031, respectively). The frequencies of haplotype GC with GD and HT patients were significantly lower than their controls (p = 0.015 and 0.030, respectively). In contrast, the frequencies of haplotype TG with GD and HT patients were significantly higher than their controls (p = 0.016 and 0.048, respectively). These findings strongly suggest that STAT4 rs7574865/rs10181656 polymorphisms increase the risk of AITD in a Chinese population.

Polymorphisms of CLEC16A Region and Autoimmune Thyroid Diseases

To investigate the association of CLEC16A gene polymorphisms and autoimmune thyroid diseases (AITDs). Six hundred sixty seven Han Chinese patients with AITDs were selected as study subjects, including 417 patients with Graves’ disease (GD), 250 patients with Hashimoto’s thyroiditis (HT) and 301 healthy control patients. Polymerase chain reaction-restriction fragment length polymorphism (RFLP) and the mass spectrometry technique were used to genotype five CLEC16A single-nucleotide polymorphisms (SNPs) (rs12708716, rs12917716, rs12931878, rs2903692, and rs6498169). Higher frequency of G allele of rs6498169 CLEC16A gene in AITDs patients [P = 0.029, odds ratio (OR) 1.29 and 95% confidence interval 1.022−1.505] was observed. In addition an association between rs6498169 and HT was observed with statistical significance (P = 0.018, OR 1.335, 95% confidence interval 1.051−1.696). Furthermore, the GG haplotype containing the major allele of (rs12708716 and rs6498169) was associated with an increased risk of HT (P = 0.0148, OR 1.344). When patients with HT and controls were compared, results from the dominant and recessive models showed that the genotype frequency of rs6498169 were at borderline levels (P = 0.054 and P = 0.05), and the other four SNPs of CLEC16A gene showed no significant association with AITDs. Our results suggest that polymorphisms rs6498169 of CLEC16A gene confers susceptibility to AITDs. We therefore disclose for the first time the association of rs6498169 SNP with AITDs.

Lack of association between polymorphisms in the UBASH3A gene and autoimmune thyroid disease: a case control study

OBJECTIVE The aim of this study was to investigate UBASH3A gene variation association with autoimmune thyroid disease and clinical features in a Chinese Han population. SUBJECTS AND METHODS A total of 667 AITD patients (417 GD and 250 HT) and 301 healthy controls were genotyped for two single nucleotide polymorphisms (SNPs) rs11203203, rs3788013 of UBASH3A gene, utilizing the Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometer (MALDI-TOF-MS) Platform. RESULTS Between the control group and AITD, GD and HT group, no statistically significant difference was observed in the genotypic and allelic frequencies of the two SNPs. There was no significant difference in allelic frequencies of the two SNPs between GD with and without ophthalmopathy. There was no significant difference in haplotype distributions between the control group and AITD, GD or HT group. CONCLUSION Rs11203203 and rs3788013 in UBASH3A gene may not be associated with AITD patients in Chinese Han population.

A case–control study of selenoprotein genes polymorphisms and autoimmune thyroid diseases in a Chinese population

BackgroundSelenium is an essential trace and there is a high selenium concentration in the thyroid gland. Selenium deficiency may impair the thyroid function. The aim of this study was to investigate the association between three selenoprotein genes polymorphisms and autoimmune thyroid diseases.MethodsWe genotyped six single-nucleotide polymorphisms (SNPs), rs6865453 in selenoprotein P gene (SELENOP), rs713041 rs2074451 rs3746165 in glutathione peroxidase 4 gene (GPX4) and rs28665122 and rs7178239 in selenoprotein S gene (SELENOS) by MassARRAY system using the chip-based matrix-assisted laser desorption ionization time-of-flight mass spectrometry technology in 1060 patients with autoimmune thyroid diseases and 938 healthy controls.ResultsMajor alleles in rs6865453 of SELENOP, rs713041, rs2074451, rs3746165 of GPX4 decreased while the major allele C in rs28665122 of SELENOS increased in AITD patients than in the control. The allele C and genotype CC in rs7178239 of SELENOS showed different trend in GD and HT patients when compared with the control. All the distribution difference showed nonsignificant. Analysis according to clinical features including ophthalmopathy, hypothyroidism and family history came out to be negative either.ConclusionsOur findings suggest non-association between three selenoprotein genes and AITD, conflicting to the positive result in another population. Different selenium nutrition status in different populations may contribute to conflicting results, the contribution of genetic variants in AITD mechanism may be another reason.

Tumor necrosis factor receptor-associated factor 1 (TRAF1) polymorphisms and susceptibility to autoimmune thyroid disease

Abstract Former studies have revealed the link between the tumor necrosis factor (TNF) receptor-associated factor 1 (TRAF1) polymorphisms and autoimmunity. In the present study, we took an opportunity to investigate the association between TRAF1 and autoimmune thyroid disease (AITD) in order to find a new susceptibility gene. A total of 1029 AITD patients [677 Graves’ disease (GD) patients and 352 Hashimoto thyroiditis (HT) patients] and 899 controls were enrolled. We used matrix-assisted laser desorption ionization-time of flight mass spectrometer (MALDI-TOF-MS) to detect the polymorphisms of rs4836834, rs10760130, rs10818488, rs2239658, rs2900180. We also explored the association between polymorphisms and clinical subphenotypes. Genotype frequencies of the five loci in all AITD patients were significantly different from those of controls. Genotype frequencies of rs10760130, rs2239658 and rs2900180 in GD patients were significantly different from controls. Allele analysis found that T allele of rs4836834, G allele of rs10760130, A allele of rs10818488, T allele of rs2239658 and T allele of rs2900180 were significantly higher in GD and AITD patients. No significant differences were found between HT patients and controls. Haplotype analysis found three haplotypes including ACAGC, TTGAT and TCGAC. ACAGC frequencies were significantly lower in GD and HT patients. However, TTGAT frequency was only significantly higher in GD patients. No significant results were found between polymorphisms and clinical subphenotypes. Our study reveals TRAF1 as a susceptibility gene of AITD in Chinese Han population.