The VDR gene confers a genetic predisposition to Graves’ disease and Graves’ ophthalmopathy in the Southwest Chinese Han population

Zhou, Fangyu; Liang, Zhongzhi; Wang, Xin; Tan, Guiqin; Wei, Wuran; Zheng, Guangbing; Ma, Xiaomin; Tian, Dan; Li, Hua; Yu, Hongsong

doi:10.1016/j.gene.2021.145750

Cited by 9 publications

(4 citation statements)

References 26 publications

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“…Moreover, the A allele (case/control: 650/1209, p = 2.62 × 10 −2 , OR = 1.20) and AA genotype (case/control: 650/1209, p = 3.45 × 10 −4 , OR = 1.87) of rs7975232 were associated with a significant increase in susceptibility to GD. In GD patients with ophthalmopathy, the frequency of the rs7975232 AA genotype was higher than in those without ophthalmopathy, suggesting that GD patients with VDR /rs7975232 are more likely to develop ocular symptoms ( Zhou et al, 2021 ). The frequency of the TT genotype of rs731236 was associated with the higher expression of VDR ( Inoue et al, 2014 ).…”

Section: The Genetic Pathogenesis Of Gdmentioning

confidence: 99%

Genetics, Epigenetics, Cellular Immunology, and Gut Microbiota: Emerging Links With Graves’ Disease

Zhou

Wang

et al. 2022

Front. Cell Dev. Biol.

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Graves’ disease (GD) is a well-known organ-specific autoimmune disease characterized by hyperthyroidism, goiter, and exophthalmos. The incidence of GD is approximately 2.0–3.0% in China and 0.5–2.0% in Western countries. Due to the complex pathogenesis and etiology of GD, current treatment methods have great side effects that seriously endanger human health. Therefore, it is particularly important to understand the pathogenesis of GD. Various studies have shown that genetics, epigenetics, cellular immunology, and gut microbiota are all involved in the development of GD. Genetically, CD25 gene and VDR gene polymorphisms are involved in the development of GD by increasing the ratio of Th17/Treg cells. Epigenetically, miR-23a-3p and lncRNA-MEG3 lead to Th17/Treg imbalance and participate in the progression of GD. Moreover, commensal microbe deletion can disrupt Th17/Treg balance and participate in the occurrence of GD. The imbalance of Th17/Treg cells induced by genetics, epigenetics, and gut microbiota plays a vital role in the pathogenesis of GD. Therefore, this article reviews the role of genetics, epigenetics, cellular immunology, and gut microbiota in the pathogenic mechanism of GD. This may lead to the development of novel therapeutic strategies and providing promising therapeutic targets.

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Section: The Genetic Pathogenesis Of Gdmentioning

confidence: 99%

Genetics, Epigenetics, Cellular Immunology, and Gut Microbiota: Emerging Links With Graves’ Disease

Zhou

Wang

et al. 2022

Front. Cell Dev. Biol.

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“…The annual incidence rate is approximately 20−30/1,000,000 2 . Although the pathogenesis of GD has not been fully elucidated, it is believed to be the result of the interaction between genetic susceptibility and environmental factors 3,4 . Therefore, the identification of genes and sites contributing to GD susceptibility is an important issue in the study of the pathogenesis of this disease.…”

Section: Introductionmentioning

confidence: 99%

Association of genetic variations in FoxP3 gene with Graves' disease in a Southwest Chinese Han population

Tan,

Zheng,

et al. 2023

Immunity Inflam & Disease

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BackgroundGraves' disease (GD) is a T cell‐mediated organ‐specific autoimmune disease. Forkhead box P3 (FoxP3) is an excellent marker for the induction and development of regulatory T cells (Tregs). Recent studies showed that single‐nucleotide polymorphisms (SNPs) in the FoxP3 gene were associated with the increased susceptibility to several autoimmune diseases. In the present study, we investigated the association of FoxP3 gene polymorphisms with GD in a Southwest Chinese Han population.MethodsA two‐stage case‐control study was performed in 890 healthy controls (male, 282; female, 608) and 503 patients with GD (male, 138; female, 365). Four SNPs (rs3761548, rs3761549, rs3761547, and rs2280883) were genotyped by the polymerase chain reaction‐restriction fragment length polymorphism assay. The χ2 test was used to compare the genotype distributions and allele frequencies between GD patients and healthy controls.ResultsIn the first stage, the significantly increased frequencies of the A allele (p = .031, odds ratio [OR] = 1.635) and AA genotype (p = .023, OR = 3.257), together with a significantly decreased frequency of the C allele (p = .031, OR = 0.611) of FoxP3/rs3761548 were found in female patients with GD. None of the other FoxP3 SNPs was associated with GD susceptibility. Subsequent validation and combination of data confirmed the association between FoxP3/rs3761548 and the female patients with GD (A allele: p < .001, OR = 1.672; AA genotype: p = .005, OR = 2.488; CC genotype: p = .001, OR = 0.622; C allele: p < .001, OR = 0.615, respectively).ConclusionOur findings suggest that FoxP3/rs3761548 is significantly associated with female GD patients in a Southwest Chinese Han population.

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“…In the past decade, increasing evidence has shown that genetic susceptibility plays a crucial role in the pathogenesis of GD and GO (21)(22)(23)(24), but the associated risk alleles in a single gene are generally insufficient to cause disease. Moreover, several studies have performed Human leukocyte antigen (HLA), cytotoxic T lymphocyte antigen-4 (CTLA4), Interleukin (IL) -23 receptor (IL23R), and TSHR genotyping on GO and non-GO patients in GD patients.…”

Section: Introductionmentioning

confidence: 99%

Emerging Insights Into the Role of Epigenetics and Gut Microbiome in the Pathogenesis of Graves’ Ophthalmopathy

Wang

et al. 2022

Front. Endocrinol.

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Graves’ Ophthalmopathy (GO) is an organ-specific autoimmune disease that is often characterized by infiltration of orbital tissues and is considered as the most common extra-thyroid manifestation of Graves’ disease (GD). Although genetic susceptibility has been found to be critical for the phenotype of GO, the associated risk alleles in a single gene are generally insufficient to cause the disease. Accruing evidence has shown that epigenetic disorders can act as the potentially missing link between genetic risk and clinically significant disease development. Abnormal epigenetic modifications can lead to pro-inflammatory cascades and activation of orbital fibroblasts (OFs) by promoting the various inflammatory response pathways and regulating the diverse signaling molecules that are involved in the fibrogenesis and adipogenesis, thereby leading to the significant expansion of orbital tissues, fibrosis and inflammation infiltration. Additionally, emerging evidence has shown that the gut microbiome can possibly drive the pathogenesis of GO by influencing the secretion of Thyrotropin receptor antibody (TRAb) and T-helper 17 (Th17)/regulatory T cells (Treg) imbalance. This paper describes the latest epigenetic research evidence and progress made in comprehending the mechanisms of GO development, such as DNA methylation, histone modification, non-coding RNAs, and the gut microbiome.

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The VDR gene confers a genetic predisposition to Graves’ disease and Graves’ ophthalmopathy in the Southwest Chinese Han population

Cited by 9 publications

References 26 publications

Genetics, Epigenetics, Cellular Immunology, and Gut Microbiota: Emerging Links With Graves’ Disease

Genetics, Epigenetics, Cellular Immunology, and Gut Microbiota: Emerging Links With Graves’ Disease

Association of genetic variations in FoxP3 gene with Graves' disease in a Southwest Chinese Han population

Emerging Insights Into the Role of Epigenetics and Gut Microbiome in the Pathogenesis of Graves’ Ophthalmopathy

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