Ni Yan

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.

RNASET2 tag SNP but not CCR6 polymorphisms is associated with autoimmune thyroid diseases in the Chinese Han population

BackgroundPolymorphisms of the CC chemokine receptor 6 (CCR6) and RNASET2 tag SNP have been shown to be associated with the susceptibility to several immune-related diseases. This study was conducted to identify the association of CCR6 and RNASET2 tag SNP with autoimmune thyroid diseases (AITDs) in the Chinese Han population.MethodsWe enrolled 1061 patients with AITDs, including 701 patients with Graves’ disease (GD) and 360 patients with Hashimoto’s thyroiditis (HT), and 938 healthy individuals for a case–control genetic association study. Three CCR6 single nucleotides polymorphisms (SNPs) (rs3093023/rs3093024/rs6902119) and one tagging SNP (rs9355610) within RNASET2 gene were selected for genotyping by multiplex polymerase chain reaction (PCR) and ligase detection reaction (LDR).ResultsThe frequency of rs9355610 genotypes in the patients with GD differed significantly from that in the controls (p = 0.017). The frequency of the minor G allele of rs9355610 was significantly higher in the GD patients than in the healthy controls (p = 0.005, OR = 1.225, 95% CI:1.063-1.412). However, we could not find significant differences in the genotype or allele frequencies of HT patients compared with healthy controls. After gender stratification, the frequency of the minor G allele in both male and female GD patients was significantly higher than that in the healthy controls (p = 0.036, OR = 1.308, 95% CI:1.017-1.684 ; p = 0.048, OR = 1.19, 95% CI:1.001-1.413; respectively);. Furthermore, the frequency of haplotype AT in GD patients was significantly lower than that in their control groups (p = 0.003) and showed a protective effect against GD (OR = 0.806, 95% CI: 0.699-0.929). The frequency of haplotype GT in GD patients was significantly higher than that in their control groups (p = 0.048), indicating that GT was the risk haplotype to GD (OR = 1.267, 95% CI: 1.001-1.603). There were no significant differences in the allele or genotype frequencies of three SNPs of CCR6 (rs3093023/rs3093024/ rs6902119) gene between GD patients, HT patients and controls.ConclusionsOur results suggest that the rs9355610 tag SNP of RNASET2 gene is positively associated with susceptibility to GD in the Chinese Han population. No association was found for the tested CCR6 SNPs.

The haplotype of UBE2L3 gene is associated with Hashimoto’s thyroiditis in a Chinese Han population

BackgroundThe ubiquitin conjugating enzyme E2L3 (UBE2L3) gene is associated with susceptibility to many autoimmune diseases. The aim of this study was to investigate the association between UBE2L3 gene and autoimmune thyroid diseases (AITDs) and their clinical phenotypes.MethodsWe genotyped five single-nucleotide polymorphisms (SNPs) rs131654, rs5754217, rs2298428, rs140489 and rs5998672 of UBE2L3 gene in case groups including 1028 patients with AITDs [676 cases of Graves’ disease (GD) and 352 cases of Hashimoto’s thyroiditis (HT)] and control group including 897 healthy individuals.The genotyping was performed with the method of polymerase chain reaction-ligase detection reaction (PCR-LDR).ResultsThe frequencies of allele and genotype of five SNPs in gene UBE2L3 showed no statistically significant difference between case groups and control group, respectively. Moreover, no significant differences in frequencies of allele and genotype of five SNPs of the gene were found between clinical subphenotypes of AITDs and control group. Such subphenotypes included GD, HT, and thyroid associated ophthalmopathy (TAO). The negative results were also found in the frequency of other haplotypes of the gene except the haplotype of TCGGC, which was significantly higher in HT group than in control group (P = 0.031, OR = 1.441).ConclusionsThe present findings indicate that TCGGC haplotype is associated with an increased risk of HT and UBE2L3 gene is likely to be a susceptibility factor to HT in a 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.

Prevalence and independent risk factors of depression in Chinese patients with type 2 diabetes: a systematic review and meta-analysis

Abstract Background Studies of the prevalence of depression in patients with type 2 diabetes in China have reported inconsistent findings. The purpose of this study was to assess the prevalence and independent risk factors of depression in patients with type 2 diabetes in China. Methods We did a systematic review and meta-analysis of papers published in PubMed (1980–2016), Embase (1980–2016), China National Knowledge Infrastructure (1999–2016), and Wanfang Medical database (1998–2016). We selected population-based, cross-sectional studies investigating the prevalence of depression in patients with type 2 diabetes in China. We used a random-effects meta-analysis to pool the prevalence and relative risks (RR) with 95% CIs. This study was registered at PROSPERO, number CRD42016039795. Findings 26 studies published between May, 2003, and February, 2016, were included. The studies included 66 475 patients with type 2 diabetes in China. A meta-analysis of six studies comparing the depression prevalence in diabetes patients and healthy controls suggested that type 2 diabetes was associated with a doubled risk of depression in Chinese people (RR 2·06; 95% CI 1·46–2·92; p 1c (RR 1·44, 95% CI 1·11–1·88; p=0·0068), and use of insulin (RR 2·08, 95% CI 1·28–3·37; p=0·0030). Interpretation We found a high prevalence of depression in Chinese patients with type 2 diabetes. Patients with diabetes and depression should receive more attention than at present in the medical settings of China and effective interventions to decrease depression risk in patients with diabetes are needed. Funding National Natural Science Foundation of China (number 81471004).

Polymorphisms of IKZF3 Gene and Autoimmune Thyroid Diseases: Associated with Graves’ Disease but Not with Hashimoto’s Thyroiditis

Background/Aims: The IKZF3 gene encodes a zinc-finger protein that plays an important role in the proliferation and differentiation of B lymphocytes. Autoimmune thyroid diseases (AITDs), mainly include Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are probably caused by the aberrant proliferation of B cells. The objective of this study was to explore the association between IKZF3 polymorphisms and AITDs. Methods: We examined 915 AITD patients (604 GD and 311 HT) and 814 healthy controls. IKZF3 variants (rs2941522, rs907091, rs1453559, rs12150079 and rs2872507) were tested by PCR-ligase detection reaction. Results: It was manifested that that the minor alleles of the five loci increased susceptibility to GD (p<0.05 for rs2941522, and p<0.01 for rs907091, rs1453559, rs12150079 and rs2872507) but in HT patients, these loci showed no significant difference compared with controls. Similarly, the genotype distributions of GD patients manifested obvious differences in all these loci compared with the control group, whereas no statistical differences were observed between HT patients and controls. Furthermore, bioinformatics tools were used to analyze rs1453559, rs12150079 and rs907091. These variants were believed to be the transcription regulator. Conclusion: It is the first time we reported the association between the IKZF3 polymorphisms and GD, indicating that IKZF3 gene tends to bean important risk factor for the development of GD.

Incidence and temporal trends of type 1 diabetes in China: a systematic review and meta-analysis

Abstract Background Studies of type 1 diabetes incidence in China have conflicting findings, and the epidemiology of type 1 diabetes in China is unclear. We aimed to assess the incidence and epidemiology of type 1 diabetes in relation to age, sex, and geographical area in mainland China. Methods In this systematic review and meta-analysis, we searched Pubmed (Jan 1, 1980, to May 18, 2016), Embase (Jan 1, 1980 to May 18, 2016), China National Knowledge Infrastructure (Jan 1, 1999, to May 20, 2016), and Wanfang Medical Database (Jan 1, 1998, to May 19, 2016) to identify population-based studies of type 1 diabetes incidence in mainland China. Only population-based studies with data on the incidence of type 1 diabetes in mainland China were included, and studies with overlapping data from included studies were excluded. We extracted data from the published reports and used random-effects meta-analysis to pool the incidence and incidence rate ratios (IRRs) with 95% CIs. We used the Q statistic and I 2 method to assess heterogeneity, and also did subgroup analyses by sex, age, and geographical area. Additionally, we used time trends to explore the difference in incidence over time. This study is registered with PROSPERO, number CRD42016039284. Findings We identified 816 reports from the search and included 19 reports of population-based studies published between 1994 and 2015 in the analysis. Overall incidence of type 1 diabetes in mainland China was 0·74 (95% CI 0·55–1·00) per 100 000 person-years between 1980 and 2013. Incidence (per 100 000 person-years) increased rapidly from 0·57 (0·43–0·75) in 1990 to 1·04 (0·64–1·68) in 2000 and 3·36 (1·66–6·82) in 2010 (p Interpretation To our knowledge, this is the first systematic review and meta-analysis to confirm the increasing incidence of type 1 diabetes over time in mainland China. Obvious disparities in incidence by sex, age, and geographical areas exist. Funding National Natural Science Foundation of China (81471004).

Prevalence of latent autoimmune diabetes in adults in China: a systematic review and meta-analysis

Abstract Background Studies of the prevalence of latent autoimmune diabetes in adults in China have reported inconsistent findings. We did a systematic review and meta-analysis to estimate the prevalence of latent autoimmune diabetes in adults in China. Methods For the systematic review, we searched PubMed, Embase, China Knowledge Resource Integrated Database, and Wanfang Medicine Database to identify studies investigating the prevalence of latent autoimmune diabetes in adults in China. In our meta-analysis we included hospital-based studies that recruited patients with newly diagnosed (less than 1 year from diagnosis) type 2 diabetes or population-based studies, which assessed the prevalence of latent autoimmune diabetes in adults in China and used a radioimmunoassay to test for glutamic acid decarboxylase autoantibodies. Subgroup analyses were done by study design, sex, and types of autoantibodies. Random-effects meta-analysis was used to pool the prevalence rate with 95% CIs. Ethical approval was granted by the ethical committee of our hospital This study was registered at PROSPERO, number CRD42016040163. Findings 12 studies with a total of 21 576 individuals were included. There were three population-based studies and nine hospital-based studies recruiting patients with newly diagnosed types 2 diabetes. The meta-analysis of 12 studies showed that the prevalence of latent autoimmune diabetes in adults in Chinese patients with type 2 diabetes was 7·4% (95% CI 6·5–8·5; 21 576 participants from 12 studies), which was similar to that in white populations (6·8%, 5·6–8·3; 28 415 participants from 15 studies). The prevalence of latent autoimmune diabetes in adults from the population-based studies was 6·7% (95% CI 5·4–8·3; 12 144 participants from three studies) and the prevalence of latent autoimmune diabetes in adults from hospital-based studies was 7·8% (6·9–8·8; 9432 participants from nine studies). The prevalence of latent autoimmune diabetes in adults in men was 7·9% (95% CI 6·2–10·0; 10 947 participants from ten studies) and in women was 7·0% (5·7–8·5; 9440 participants from ten studies). Subgroup analysis by types of autoantibodies suggested that glutamic acid decarboxylase autoantibodies was the highest prevalence (5·9%, 95% CI 5·2–6·8; 24 068 participants from 12 studies), followed by islet cell antibodies (2·4%, 1·5–3·8; 678 participants from two studies), insulin autoantibodies (2·1%, 1·4–3·2; 6559 participants from six studies), zinc transporter type 8 antibodies (1·7%, 1·5–2·1; 7059 participants from two studies), and protein tyrosine phosphatase-like IA-2 autoantibodies (1·7%, 1·2–2·4; 16 748 participants from 5 studies). The prevalence of latent autoimmune diabetes in adults diagnosed by non-glutamic acid decarboxylase autoantibodies in China was 1·7% (95% CI 1·0–2·8; 18 671 participants from eight studies). Interpretation Our finding provides evidence for a high prevalence of latent autoimmune diabetes in adults in China. Additionally, screening of latent autoimmune diabetes in adults with multiple diabetes-associated autoantibodies is necessary in China. Funding None.