METTL3 gene polymorphisms contribute to susceptibility to autoimmune thyroid disease

Song, Ronghua; Liu, Xuerong; Gao, Chaoqun; Zhang, Jinan

doi:10.1007/s12020-020-02503-1

Cited by 12 publications

(8 citation statements)

References 30 publications

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“…WTAP interacts with METTL3 and METTL14, then localizes them into nuclear speckles ( 29 , 30 ). Notably the SNPs located in these m6A methyltransferases are reportedly associated with disease susceptibility via m6A methylation and related biological processes ( 19 , 20 , 31 ). To the best of our knowledge, the current study is the first to investigate associations between polymorphic variants of the m6A methyltransferase genes METTL3 , METTL14 , and WTAP and PTB susceptibility.…”

Section: Discussionmentioning

confidence: 99%

Roles of the m6A methyltransferases METTL3, METTL14, and WTAP in pulmonary tuberculosis

Zhang

Li²,

Wang³

et al. 2022

Front. Immunol.

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ObjectiveThe aim of the current study was to investigate the contributing role of gene variation and transcription levels among the m6A methyltransferases METTL3, METTL14, and WTAP in pulmonary tuberculosis (PTB).MethodsA case-control study including 461 PTB patients and 467 normal controls was designed for genotyping. Three SNPs in METTL3 (rs1061027, rs1139130, rs1061026), three SNPs in METTL14 (rs62328061, rs4834698, rs1064034), and two SNPs in WTAP (rs1853259, rs11752345) were genotyped via the SNPscan™ technique. METTL3, METTL14, and WTAP transcription levels were determined in 78 PTB patients and 86 controls via quantitative real-time reverse-transcription PCR.ResultsFrequencies of the METTL14 rs62328061 GG genotype, WTAP rs11752345 CT genotype, and T allele were significantly increased in PTB patients compared to controls. An increased risk of rs62328061 was detected in a recessive model, and a decreased risk of rs11752345 was detected in a dominant model in the PTB group. METTL3 gene variation was not associated with PTB risk. The METTL3 rs1139130 GG genotype was significantly increased with drug resistance, and the G allele was significantly decreased with drug-induced liver injury in PTB patients. A reduced frequency of the METTL14 rs62328061 G allele was associated with leukopenia, a reduced frequency of the WTAP rs11752345 T allele was associated with sputum smear positivity, and a higher frequency of the METTL14 rs4834698 TC genotype was evident in PTB patients with hypoproteinemia. Compared to controls, METTL3, METTL14, and WTAP transcription levels in PTB patients were significantly decreased, and the level of WTAP was increased in PTB patients with drug resistance. METTL3 level was negatively associated with erythrocyte sedimentation rate and aspartate aminotransferase, and METTL14 level was negatively correlated with alanine aminotransferase and aspartate aminotransferase.ConclusionMETTL14 rs62328061 and WTAP rs11752345 variants were associated with the genetic background of PTB, and METTL3, METTL14, and WTAP levels were abnormally decreased, suggesting that these m6A methyltransferases may play important roles in PTB.

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Section: Discussionmentioning

confidence: 99%

Roles of the m6A methyltransferases METTL3, METTL14, and WTAP in pulmonary tuberculosis

Zhang

Li²,

Wang³

et al. 2022

Front. Immunol.

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“…As a key RNA methylation modification enzyme, METTL3 is reported to regulate the mRNA and protein levels of several key molecules and plays a key role in diverse life processes ( 15 ). Although we have previously shown that METTL3 polymorphisms confer risk for the susceptibility of GD ( 18 ) and mRNA m6A modification is known to regulate immune cell differentiation and immune response ( 10 – 12 ) and is involved in the development of some autoimmune diseases ( 16 , 17 ). The mechanisms underlying the effects of m6A modification on autoimmune diseases including GD are still incompletely understood and require more in-depth studies.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, some studies found that polymorphisms of METTL3 and fat mass and obesity associated (FTO) genes are involved in the pathogenesis of some autoimmune diseases, such as rheumatoid arthritis (RA) (16) and latent autoimmune diabetes (LADA) (17). Our recent study also uncovered that METTL3 polymorphisms are involved in the pathogenesis of AITDs, including GD (18). However, the mechanism underlying the involvement of mRNA m 6 A modification in GD development is still incompletely understood.…”

Section: Introductionmentioning

confidence: 92%

METTL3 Is Involved in the Development of Graves’ Disease by Inducing SOCS mRNA m6A Modification

et al. 2021

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ObjectiveEpigenetic modifications in RNA are known to play critical roles in cell differentiation through regulating expressions of some key genes including members of the suppressor of cytokine signaling (SOCS) family. The present study aimed to unveil the relationship of SOCS mRNA methylation induced by methyltransferase like 3 (METTL3) with Graves’ disease (GD).MethodsDifferently expressed genes (DEG) in GD tissues were identified using microarray analysis and further validated using CD4+ T cell microarray of GD tissues and isolated peripheral blood mononuclear cells (PBMCs). Furthermore, expressions of METTL3 targeted genes were detected using METTL3 knock-down experiment in RAW264.7 cells.ResultsHigh throughput microarrays revealed that METTL3 and SOCS molecules were aberrantly expressed in thyroid tissues and CD4+T cells of GD compared to the controls. Bioinformatic analysis was undertaken by searching databases of found genes of the SOCS family that possessed many mRNA m6A modification loci. METTL3 knock-down experiment revealed that expressions of SOCS family members SOCS1, SOCS2, SOCS4, SOCS5, and SOCS6 were increased after METTL3 knock-down.ConclusionsFor the first time, the present study revealed the relationship between m6A modification and GD and indicated that METTL3 may be involved in the development of GD by inducing mRNA m6A methylation modification of SOCS family members.

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“…Copy number variations (CNVs), as a main type of structure variation (SV) caused by genomic rearrangement, mainly include deletion and duplication of sub-microscopic but large genomic segments ranging from 1 kb to 3 Mb ( Redon et al, 2006 ). Single-nucleotide polymorphisms (SNPs) have been recognized to be involved in many autoimmune diseases (AIDs) ( Song et al, 2021a ; Song et al, 2021b ; Jiang et al, 2021 ); however, CNVs containing more nucleotide content per genome than SNPs are responsible for a large proportion of human genetic variation and show an importance in genetic diversity and evolution ( Redon et al, 2006 ; Cleynen et al, 2016 ). Thus, more attention has been paid to the research of CNVs in diseases.…”

Section: Introductionmentioning

confidence: 99%

“…Although majority of human genetic variations do not contribute to overt diseases ( Tomer and Davies, 2003 ), some genetic variations including SNPs, nucleotide insertions/deletions, structural variations, and CNVs are known to link to several AIDs during the past few decades and are of importance in the susceptibility to AIDs and the potential therapeutic responses to medicines ( Iafrate et al, 2004 ; Redon et al, 2006 ). Studies have revealed that some SNPs are related to AIDs and could be genetic mechanisms underlying the development of AIDs ( Song et al, 2021a ; Song et al, 2021b ; Jiang et al, 2021 ). Structural variations including complex rearrangement of segments with sizes of thousands to millions of base pairs have been recognized as a rich source of genetic diversity.…”

Section: Introductionmentioning

confidence: 99%

An Update Evolving View of Copy Number Variations in Autoimmune Diseases

et al. 2022

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Autoimmune diseases (AIDs) usually share possible common mechanisms, i.e., a defect in the immune tolerance exists due to diverse causes from central and peripheral tolerance mechanisms. Some genetic variations including copy number variations (CNVs) are known to link to several AIDs and are of importance in the susceptibility to AIDs and the potential therapeutic responses to medicines. As an important source of genetic variants, DNA CNVs have been shown to be very common in AIDs, implying these AIDs may possess possible common mechanisms. In addition, some CNVs are differently distributed in various diseases in different ethnic populations, suggesting that AIDs may have their own different phenotypes and different genetic and/or environmental backgrounds among diverse populations. Due to the continuous advancement in genotyping technology, such as high-throughput whole-genome sequencing method, more susceptible variants have been found. Moreover, further replication studies should be conducted to confirm the results of studies with different ethnic cohorts and independent populations. In this review, we aim to summarize the most relevant data that emerged in the past few decades on the relationship of CNVs and AIDs and gain some new insights into the issue.

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METTL3 gene polymorphisms contribute to susceptibility to autoimmune thyroid disease

Cited by 12 publications

References 30 publications

Roles of the m6A methyltransferases METTL3, METTL14, and WTAP in pulmonary tuberculosis

Roles of the m6A methyltransferases METTL3, METTL14, and WTAP in pulmonary tuberculosis

METTL3 Is Involved in the Development of Graves’ Disease by Inducing SOCS mRNA m6A Modification

An Update Evolving View of Copy Number Variations in Autoimmune Diseases

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