Synergistic effects of BTN3A1, SHP2, CD274, and STAT3 gene polymorphisms on the risk of systemic lupus erythematosus: a multifactorial dimensional reduction analysis

Tang, Yang-Yang; Xu, Wang-Dong; Fu, Lu; Liu, Xiao-Yan; Huang, An-Fang

doi:10.1007/s10067-023-06765-8

Cited by 4 publications

(2 citation statements)

References 45 publications

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“…It has been implicated in autoimmune diseases, diabetes mellitus, multiple sclerosis, and cancer ( 27 ). Several SNPs, including rs1796520, rs3857550, rs3208733, rs6912853, and rs10456045, of BTN3A1 have been associated with SLE patients ( 28 , 29 ). Our MR analysis provides evidence that the top SNP rs149123117, located in BTN3A1, is a protective factor against SS, possibly linked to the up-regulation of cg22068371 methylation leading to increased BTN3A1 protein levels.…”

Section: Discussionmentioning

confidence: 99%

Identification of drug targets for Sjögren’s syndrome: multi-omics Mendelian randomization and colocalization analyses

Bai,

Wang,

Feng

et al. 2024

Front. Immunol.

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BackgroundTargeted therapy for Sjögren’s syndrome (SS) has become an important focus for clinicians. Multi-omics-wide Mendelian randomization (MR) analyses have provided new ideas for identifying potential drug targets.MethodsWe conducted summary-data-based Mendelian randomization (SMR) analysis to evaluate therapeutic targets associated with SS by integrating DNA methylation, gene expression and protein quantitative trait loci (mQTL, eQTL, and pQTL, respectively). Genetic associations with SS were derived from the FinnGen study (discovery) and the GWAS catalog (replication). Colocalization analyses were employed to determine whether two potentially relevant phenotypes share the same genetic factors in a given region. Moreover, to delve deeper into potential regulation among DNA methylation, gene expression, and protein abundance, we conducted MR analysis to explore the causal relationship between candidate gene methylation and expression, as well as between gene expression and protein abundance. Drug prediction and molecular docking were further employed to validate the pharmacological activity of the candidate drug targets.ResultsUpon integrating the multi-omics data, we identified three genes associated with SS risk: TNFAIP3, BTN3A1, and PLAU. The methylation of cg22068371 in BTN3A1 was positively associated with protein levels, consistent with the negative effect of cg22068371 methylation on the risk of SS. Additionally, positive correlations were observed between the gene methylation of PLAU (cg04939496) and expression, as well as between expression and protein levels. This consistency elucidates the promotional effects of PLAU on SS risk at the DNA methylation, gene expression, and protein levels. At the protein level, genetically predicted TNFAIP3 (OR 2.47, 95% CI 1.56–3.92) was positively associated with SS risk, while BTN3A1 (OR 2.96E-03, 95% CI 2.63E-04–3.33E-02) was negatively associated with SS risk. Molecular docking showed stable binding for candidate drugs and target proteins.ConclusionOur study reveals promising therapeutic targets for the treatment of SS, providing valuable insights into targeted therapy for SS. However, further validation through future experiments is warranted.

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Section: Discussionmentioning

confidence: 99%

Identification of drug targets for Sjögren’s syndrome: multi-omics Mendelian randomization and colocalization analyses

Bai,

Wang,

Feng

et al. 2024

Front. Immunol.

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show abstract

“…It has been implicated in autoimmune diseases, diabetes mellitus, multiple sclerosis, and cancer (27). Several SNPs, including rs1796520, rs3857550, rs3208733, rs6912853, and rs10456045, of BTN3A1 have been associated with SLE patients (28,29). Our MR analysis provides evidence that the top SNP rs149123117, located in BTN3A1, is a protective factor against SS, possibly linked to the up-regulation of cg22068371 methylation leading to increased BTN3A1 protein levels.…”

Section: Discussionmentioning

confidence: 64%

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Type I interferon associated epistasis may contribute to early disease-onset and high disease activity in juvenile-onset lupus

Renaudineau,

Charras,

Natoli

et al. 2024

Clinical Immunology

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Synergistic effects of BTN3A1, SHP2, CD274, and STAT3 gene polymorphisms on the risk of systemic lupus erythematosus: a multifactorial dimensional reduction analysis

Cited by 4 publications

References 45 publications

Identification of drug targets for Sjögren’s syndrome: multi-omics Mendelian randomization and colocalization analyses

Identification of drug targets for Sjögren’s syndrome: multi-omics Mendelian randomization and colocalization analyses

DataSheet_1.zip

Type I interferon associated epistasis may contribute to early disease-onset and high disease activity in juvenile-onset lupus

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