Common genetic variants in PRRC2A are associated with both neuromyelitis optica spectrum disorder and multiple sclerosis in Han Chinese population

Zhang, Juan; Chen, Mei-Jiao; Zhao, Guodong; Li, Hongfu; Wu, Lei; Xu, Yongfeng; Liao, Yuhe; Yuan, Zengqiang; Wu, Zhi‐Ying

doi:10.1007/s00415-020-10184-z

Cited by 8 publications

(7 citation statements)

References 27 publications

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“…Based on eQTL analysis, we found that the rs2260051 may influence the mRNA expression level of PRRC2A. Interestingly, rs3130623 is in moderate linkage disequilibrium with another PRRC2A variant, rs2736157, which was recently reported to be associated with neuromyelitis optica and multiple sclerosis in a Chinses cohort ( 34 ). Thus, these PRRC2A variants may provide insight into the pathogenesis of dysregulated m6A modification in autoimmune diseases.…”

Section: Discussionmentioning

confidence: 84%

Genome-Wide Identification of N6-Methyladenosine Associated SNPs as Potential Functional Variants for Type 1 Diabetes

et al. 2022

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ObjectivesN6-methyladenosine (m6A) is essential in the regulation of the immune system, but the role that its single nucleotide polymorphisms (SNPs) play in the pathogenesis of type 1 diabetes (T1D) remains unknown. This study demonstrated the association between genetic variants in m6A regulators and T1D risk based on a case-control study in a Chinese population.MethodsThe tagging SNPs in m6A regulators were genotyped in 1005 autoantibody-positive patients with T1D and 1257 controls using the Illumina Human OmniZhongHua-8 platform. Islet-specific autoantibodies were examined by radioimmunoprecipitation in all the patients. The mixed-meal glucose tolerance test was performed on 355 newly diagnosed patients to evaluate their residual islet function. The functional annotations for the identified SNPs were performed in silico. Using 102 samples from a whole-genome expression microarray, key signaling pathways associated with m6A regulators in T1D were comprehendingly evaluated.ResultsUnder the additive model, we observed three tag SNPs in the noncoding region of the PRRC2A (rs2260051, rs3130623) and YTHDC2 (rs1862315) gene are associated with T1D risk. Although no association was found between these SNPs and islet function, patients carrying risk variants had a higher positive rate for ZnT8A, GADA, and IA-2A. Further analyses showed that rs2260051[T] was associated with increased expression of PRRC2A mRNA (P = 7.0E-13), and PRRC2A mRNA was significantly higher in peripheral blood mononuclear cell samples from patients with T1D compared to normal samples (P = 0.022). Enrichment analyses indicated that increased PRRC2A expression engages in the most significant hallmarks of cytokine-cytokine receptor interaction, cell adhesion and chemotaxis, and neurotransmitter regulation pathways. The potential role of increased PRRC2A in disrupting immune homeostasis is through the PI3K/AKT pathway and neuro-immune interactions.ConclusionThis study found intronic variants in PRRC2A and YTHDC2 associated with T1D risk in a Chinese Han population. PRRC2A rs2260051[T] may be implicated in unbalanced immune homeostasis by affecting the expression of PRRC2A mRNA. These findings enriched our understanding of m6A regulators and their intronic SNPs that underlie the pathogenesis of T1D.

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Section: Discussionmentioning

confidence: 84%

Genome-Wide Identification of N6-Methyladenosine Associated SNPs as Potential Functional Variants for Type 1 Diabetes

et al. 2022

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“…A study conducted in the Han Chinese population reported that rs2736157 AG genotype was associated with increased risk susceptibility for AQP4 + neuromyelitis optica spectrum disorder (NMOSD) (p = .03) (J. Zhang et al, 2021). As presented in Supplementary Table S10, rs2736157 was in strong LD with rs10885 (r 2 = .99), indicating the potential association between rs10885 and NMOSD.…”

Section: Discussionmentioning

confidence: 95%

“…A variety of studies have reported that the genetic variants in BAT2 were associated with susceptibility to numerous immunemediated diseases, such as rheumatoid arthritis (Singal et al, 2000), ulcerative colitis (Fernández et al, 2005), Kawasaki disease (Hsieh et al, 2010), non-Hodgkin lymphoma (Nieters et al, 2012) and multiple sclerosis (J. Zhang et al, 2021). It has been reported that the mutation in BAT2 was correlated with the antibody levels of Pseudorabies virus in pigs (Wang et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Genetic variants in BAT2 are associated with immune responsiveness to influenza vaccination

Wen

Wei

et al. 2023

Front. Genet.

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Background: Influenza is a global public health problem for its detrimental impact on human health. Annual vaccination is the most effective prevention of influenza infection. Identifying host genetic factors associated with the responsiveness to influenza vaccines can provide clues for developing more effective influenza vaccines. In this study, we aimed to explore whether the single nucleotide polymorphisms in BAT2 are associated with the antibody responses to influenza vaccines.Method: A nested case-control study was conducted in this research. 1968 healthy volunteers were enrolled and 1,582 of them from a Chinese Han population were eligible for further research. According to the hemagglutination inhibition titers of subjects against all influenza vaccine strains, a total of 227 low responders and 365 responders were included in the analysis. Six tag single nucleotide polymorphisms in the coding region of BAT2 were selected and genotyped using the MassARRAY technology platform. Univariable and multivariable analyses were conducted to evaluate the relationship between variants and antibody responses to influenza vaccination.Results: Multivariable logistic regression analysis showed that, compared with the BAT2 rs1046089GG genotype, the GA + AA genotype was correlated with decreased risk of low responsiveness to influenza vaccines after adjusting for gender and age (p = 1.12E-03, OR = .562, 95%CI: .398–.795). rs9366785 GA + AA genotype was associated with a higher risk of low responsiveness to influenza vaccination compared with the GG genotype (p = .003, OR = 1.854, 95%CI: 1.229–2.799). The haplotype consisting of BAT2 rs2280801-rs10885-rs1046089-rs2736158-rs1046080-rs9366785 CCAGAG was correlated with a higher level of antibody response to influenza vaccines compared with haplotype CCGGAG (p < .001, OR = .37, 95%CI: .23–.58).Conclusion: Genetic variants in BAT2 were statistically associated with the immune response to influenza vaccination among the Chinese population. Identifying these variants will provide clues for further research on novel broad-spectrum influenza vaccines, and improve the individualized influenza vaccination scheme.

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“…In clinical manifestations, the two sub‐types also demonstrate distinct differences and treatment responses. 32 In this regard, a previous study provided evidence that distinct genetic profiles characterize AQP4‐negative and AQP4‐positive NMOSD while also sharing common genetic determinants. 33 Our reports support the stated conclusion.…”

Section: Discussionmentioning

confidence: 98%

BLK polymorphisms and expression level in neuromyelitis optica spectrum disorder

Yin

Mehmood

et al. 2021

CNS Neurosci Ther

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Common genetic variants in PRRC2A are associated with both neuromyelitis optica spectrum disorder and multiple sclerosis in Han Chinese population

Cited by 8 publications

References 27 publications

Genome-Wide Identification of N6-Methyladenosine Associated SNPs as Potential Functional Variants for Type 1 Diabetes

Genome-Wide Identification of N6-Methyladenosine Associated SNPs as Potential Functional Variants for Type 1 Diabetes

Genetic variants in BAT2 are associated with immune responsiveness to influenza vaccination

BLK polymorphisms and expression level in neuromyelitis optica spectrum disorder

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