TNFSF4 Gene Variations Are Related to Early-Onset Autoimmune Thyroid Diseases and Hypothyroidism of Hashimoto’s Thyroiditis

Song, Ronghua; Wang, Qiong; Yao, Qiuming; Shao, Xiaorong; Li, Ling; Wang, Wen; An, Xiaofei; Li, Qian; Zhang, Jin‐an

doi:10.3390/ijms17081369

Cited by 13 publications

(9 citation statements)

References 28 publications

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“…Besides, it showed that allele C of rs1179251 increases the teenagers' risk for AITD by 39.7%. Similarly, a pervious paper of ours also reported that there is an association between TNFSF4 gene variations and AITD adolescents [ 19 ]. So these results strongly suggest that the occurrence of thyroid dysfunction in teenagers can be caused by family history, which means the genetic background.…”

Section: Discussionsupporting

confidence: 71%

Variants of Interleukin-22 Gene Confer Predisposition to Autoimmune Thyroid Disease

Song

Wang

et al. 2017

International Journal of Endocrinology

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As there are no previous studies on the interleukin-22 (IL-22) variants in autoimmune thyroid disease (AITD), the present study aimed to explore the association between polymorphisms of IL-22 and the predisposition to AITD. The study had 975 AITD patients, including 639 Graves' disease (GD) and 336 Hashimoto's thyroiditis (HT) individuals and 851 healthy cohorts. Ligase detection reaction (LDR) and direct sequencing method were used for genotyping the IL-22 gene polymorphisms at rs2046068, rs2227478, rs2227485, rs11611206, and rs1179251. In comparison to female controls, genotype CC of rs1179251 was increased in the female AITD patients. Alleles C at rs2046068, C at rs2227478, and C at rs1179251 linked to the susceptibility of HT males. Genotype CC in rs1179251 was higher in male HT. Variants at rs2046068, rs2227478, and rs1179251 were associated with the AITD teenagers. Besides, genotype GG in rs11611206 was correlated with thyroid-associated ophthalmopathy (TAO). Moreover, allele G at rs11611206 was associated with decreased risk for TAO by 28.9%. Similarly, genotype CC of rs1179251 and genotype GG of rs11611206 were associated with Graves' ophthalmopathy (GO). Allele G in rs11611206 increased people with HT towards the predisposition of hypothyroidism. In conclusion, genetic variants of IL-22 are associated with the occurrence of AITD.

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Section: Discussionsupporting

confidence: 71%

Variants of Interleukin-22 Gene Confer Predisposition to Autoimmune Thyroid Disease

Song

Wang

et al. 2017

International Journal of Endocrinology

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“…TNFSF4 , also known as OX40L , could be capable of interacting with its receptor on the late proliferation and sustained activation of T lymphocytes by extending the half-life of the cytokine mRNA ( Vogel et al, 2013 ). Previous studies have shown that genetic variants of TNFSF4/TNFRSF4 are associated with immune disorders such as Behcet’s Disease ( Lu et al, 2016 ), autoimmune thyroid diseases (AITDs; Song et al, 2016 ), and SLEs ( Cortini et al, 2017 ). We found that TNFSF4 rs7514229-T (the mutant allele) was linked to an increased risk of HCV infection, and this effect was more evident in the age, female, lower ALT level (≤ 40 U/L), lower AST level (≤ 40 U/L), HD, and PBD subgroups.…”

Section: Discussionmentioning

confidence: 99%

Genetic Variants in TNFSF4 and TNFSF8 Are Associated With the Risk of HCV Infection Among Chinese High-Risk Population

Cai

Shao

et al. 2021

Front. Genet.

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BackgroundThe tumor necrosis factor superfamily (TNFSF) and TNF receptor superfamily (TNFRSF) play important roles in the immune responses to infections. The aim of this study was to determine the impact of single nucleotide polymorphisms (SNPs) of several TNFSF/TNFRSF genes on the risk of hepatitis C virus (HCV) infection in the Chinese high-risk population.MethodsThe TNFSF4-rs1234313, TNFSF4-rs7514229, TNFSF8-rs3181366, TNFSF8-rs2295800, TNFRSF8-rs2298209, and TNFRSF8-rs2230625 SNPs were genotyped in 2309 uninfected controls, 597 subjects with spontaneous HCV clearance and 784 patients with persistent HCV infection using the TaqMan-MGB assay. The putative functions of the positive SNPs were determined using online bioinformatics tools.ResultsAfter adjusting for gender, age, high-risk population, alanine transaminase (ALT), aspartate aminotransferase (AST), IL28B-rs12979860 and rs8099917 genotypes, the non-conditional logistic regression showed that rs7514229-T, rs3181366-T, and rs2295800-C were associated with an increased risk of HCV infection (all PFDR < 0.05). Combined analysis of rs7514229-T and rs3181366-T risk alleles showed that the subjects carrying 2–4 risk alleles were more susceptible to HCV infection compared with those lacking any risk allele (all P < 0.001). Furthermore, the risk of HCV infection increased with the number of risk alleles (Ptrend < 0.001). In silico analysis showed that rs7514229, rs3181366, and rs2295800 polymorphisms may affect the transcription of mRNA by regulating miRNA binding, TF binding, and promoter activation, respectively, which may have biological consequences.ConclusionTNFSF4-rs7514229, TNFSF8-rs3181366, and TNFSF8-rs2295800 are associated with increased risk of HCV infection in the Chinese high-risk population.

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“…Three SNPs (rs10065172/rs4958847/rs13361189) of IRGM gene were selected from the Hapmap CHB data [ 15 ] with the following criteria: minor allele frequency (MAF) > 0.05, Hardy–Weinberg equilibrium (HWE) with P > 0.001, and logarithm of odds (LOD) > 3.0. These three SNPs were genotyped by PCR-based ligase detection reaction (LDR) method used in our previous studies [ 16 – 18 ]. The PCR condition was initial denaturation at 95°C for 2 min, denaturation at 94°C for 30 s, annealing at 62°C for 90 s, extension at 72°C for 1 min with 40 cycles and final extension at 65°C for 10 min.…”

Section: Methodsmentioning

confidence: 99%

Polymorphisms in Autophagy-Related Gene IRGM Are Associated with Susceptibility to Autoimmune Thyroid Diseases

Yao

Zhu

Wang

et al. 2018

BioMed Research International

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Background To date, studies have shown that polymorphisms in an autophagy-related gene, IRGM, are linked with different diseases, especially autoimmune diseases. The present study aimed to examine the roles of IRGM polymorphisms in autoimmune thyroid diseases (AITD). Methods Three polymorphisms in IRGM gene (rs10065172, rs4958847, and rs13361189) were genotyped in 1569 participants (488 with Graves' disease, 292 with Hashimoto's thyroiditis, and 789 healthy controls) using PCR-based ligase detection reaction method. Gene-disease associations were evaluated for the three SNPs. Results T allele of rs10065172, A allele of rs4958847, and C allele of rs13361189 were all higher in Graves' disease patients than controls, and the ORs were OR = 1.207 (P = 0.022), OR = 1.207 (P = 0.027), and OR = 1.200 (P = 0.027), respectively. After adjusting for sex and age, rs10065172 and rs13361189 were still associated with GD under both the allele model and dominant model, and the adjusted ORs for rs10065172 were 1.20 (P = 0.033) and 1.33 (P = 0.024), while the adjusted ORs for rs13361189 were 1.19 (P = 0.042) and 1.33 (P = 0.026), respectively. No significant difference was found between Hashimoto's thyroiditis patients and controls. Haplotype analysis found that CTA frequency was distinguishingly higher in Graves' disease patients (OR = 1.195, P = 0.030). The frequency of TCG haplotype was distinguishingly lower in AITD and Graves' disease patients (OR = 0.861, P = 0.044; OR = 0.816, P = 0.017). Conclusions Our study reveals IRGM as a susceptibility gene of AITD and Graves' disease for the first time.

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TNFSF4 Gene Variations Are Related to Early-Onset Autoimmune Thyroid Diseases and Hypothyroidism of Hashimoto’s Thyroiditis

Cited by 13 publications

References 28 publications

Variants of Interleukin-22 Gene Confer Predisposition to Autoimmune Thyroid Disease

Variants of Interleukin-22 Gene Confer Predisposition to Autoimmune Thyroid Disease

Genetic Variants in TNFSF4 and TNFSF8 Are Associated With the Risk of HCV Infection Among Chinese High-Risk Population

Polymorphisms in Autophagy-Related Gene IRGM Are Associated with Susceptibility to Autoimmune Thyroid Diseases

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