Polymorphisms in the CIITA −168A/G (rs3087456) and CIITA +1614G/C (rs4774) may influence severity in multiple sclerosis patients

Pereira, Valeska Martinho; Fontes-Dantas, Fabrícia Lima; Paradela, Eduardo Ribeiro; Malfetano, Fabíola Rachid; Scherpenhuijzen, Simone; Mansur, Letícia F.; Luiz, Ronir Raggio; Oliveira, André Peres De; Farinhas, João Gabriel Dib; Maiolino, Ângelo; Alves-Leon, Soniza Vieira

doi:10.1590/0004-282x20190026

Cited by 7 publications

(7 citation statements)

References 42 publications

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“…In Brazilian patients, a population characterized by ethnic admixture, HLA-DRB1*15:01, has been shown to confer MS susceptibility based on clinical features 16 . Additionally, genetic predictors of MS susceptibility, disease activity, and severity have been identified in two other studies of Brazilian patients 11,17 .…”

Section: Discussionmentioning

confidence: 99%

“…The number of BH and enhanced lesion (EL) were counted. Following the modified 2017 McDonald criteria, lesion locations were recorded as periventricular, justacortical (subcortical/cortical), posterior fossa, and spinal cord 11 . Two observers with 25 and 10 years of experience who were blinded to patient information counted and measured the lesions visually/manually, without the use of an automatic tool.…”

Section: Magnetic Resonance Imaging Evaluationmentioning

confidence: 99%

“…3. Another work suggests that the polymorphisms CIITA -168AA, CIITA +1614GG, and CIITA +1614 GC are associated with a better clinical course of MS in Brazilian patients with the disease 11 .…”

Section: Introductionmentioning

confidence: 98%

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HLA-DQA1*04:01 is related to a higher multiple sclerosis lesion load on T2/Flair MRI sequences

Noro

Alves-Leon

Fontes-Dantas

et al. 2021

Arq. Neuro-Psiquiatr.

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Background: The genetic predisposition to multiple sclerosis (MS) is associated with HLA alleles, especially HLA-DRB1*15:01. Objective: To identify associations between findings in magnetic resonance imaging (MRI) and genetic features in a Brazilian cohort of patients with MS. Methods: We retrospectively studied data from 95 consecutive patients with MS. Two independent observers who were blinded to the clinical data identified black holes and enhanced lesions on T1 MRI sequences, and counted and measured contrast-enhanced lesions on T2 and Flair (fluid attenuation inversion recovery) sequences. Cases were classified according to lesion size, number, and volume. The HLA-DRB1, HLA-DQB1, and HLA-DQA1 alleles, and the rs4774, rs3087456, rs6897932, rs731236, and rs1033182 single nucleotide polymorphisms were identified by polymerase chain reaction amplification with sequence-specific primers using the One Lambda Inc. Kit, Canoga Park, CA, USA. Results: Patients with the HLA-DQA1*04:01 allele had lesion load (adjusted for age, sex, and MS duration) above median compared with patients with other HLA-DQA1 alleles (p=0.02). There were no differences among all the other HLA alleles and single nucleotide polymorphisms and lesion load. Conclusions: The correlation of the HLA-DQA1*04:01 allele with a higher lesion load on T2/Flair MRI sequences suggests that the presence of this allele is associated with the risk of greater MS severity.

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Section: Discussionmentioning

confidence: 99%

Section: Magnetic Resonance Imaging Evaluationmentioning

confidence: 99%

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HLA-DQA1*04:01 is related to a higher multiple sclerosis lesion load on T2/Flair MRI sequences

Noro

Alves-Leon

Fontes-Dantas

et al. 2021

Arq. Neuro-Psiquiatr.

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“…Reportedly, genetic mutation on MHC class II regulatory genes can impress effects on expression of MHC class II gene ( Lochamy et al , 2007 ). As for genotype–phenotype correlation, genetic variants on CIITA , CREB1 , NFYC , RFXANK , and RFXAP have been related to squamous cell lung carcinoma, liver cancer, chronic hepatitis B, systemic lupus erythematosus, multiple sclerosis, lymphocyte syndrome, rheumatoid arthritis, and type 2 diabetes ( Kishimoto et al , 2005 ; Takenoyama et al , 2006 ; Zhang et al , 2007 ; Bronson et al , 2011 ; Wang et al , 2013 ; Xu et al , 2018 ; Pereira et al , 2019 ). Given its indispensable role in the expression of MHC class II gene, MHC class II regulatory genes may be the rudimentary candidates of susceptible genes for NPC.…”

Section: Discussionmentioning

confidence: 99%

Association between variant alleles of major histocompatibility complex class II regulatory genes and nasopharyngeal carcinoma susceptibility

Zhou

et al. 2020

European Journal of Cancer Prevention

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Major histocompatibility complex (MHC) class II regulatory genes play a paramount role in immune response that can exert a predominant influence on clinical outcome of Epstein–Barr virus infection consistently assumed as the main pathogenetic factor for nasopharyngeal carcinoma. To elucidate the relationship between allelic variants of MHC class II regulatory genes and susceptibility to nasopharyngeal carcinoma, a total of 28 polymorphic loci at MHC class II regulatory genes, involving CIITA, CREB1, RFX family genes (RFX5, RFXAP, and RFXANK), and NFY family genes (NFYA, NFYB, and NFYC), were genotyped by multiplex SNaPshot minisequencing in 137 patients with nasopharyngeal carcinoma and 107 healthy controls from the southern Chinese population. Allelic analysis disclosed that rs7404873, rs6498121, rs6498126, and rs56074043 shared correlations with nasopharyngeal carcinoma (P trend < 0.05). Further, rs6498126 on CIITA was independently associated with the risk of developing nasopharyngeal carcinoma (CC vs. GG, odds ratio: 7.386, 95% confidence interval: 1.934–28.207, P trend < 0.01). Conversely, rs7404873 on CIITA and rs56074043 on NFYB manifested epistatic interaction to decreased susceptibility of nasopharyngeal carcinoma (rs7404873, TT vs. GG, odds ratio: 0.256, 95% confidence interval: 0.088–0.740, P trend < 0.05; rs56074043, AA vs. AG, odds ratio: 0.341, 95% confidence interval: 0.129–0.900, P trend < 0.05). Additionally, bioinformatics analysis revealed that the three variants were transcriptional regulatory in function and might impact the expression of nearby genes. The findings suggested genetic variants on MHC class II regulatory genes contributed to nasopharyngeal carcinoma susceptibility and might provide new insights for screening high-risk population.

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“…Positive clones were screened and sequenced (Sunny, Shanghai, China). Ten randomly picked clones for each amplified locus were sequenced using the ABI3730xl platform 37 …”

Section: Methodsmentioning

confidence: 99%

UHRF1 shapes both the trophoblast invasion and decidual macrophage differentiation in early pregnancy

Liu

Wang

et al. 2022

The FASEB Journal

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Trophoblasts play critical roles in establishment and maintenance of a normal pregnancy. Their dysfunction in early pregnancy is closely related to pregnancy‐related diseases, including recurrent pregnancy loss (RPL). Epigenetic modifications dynamically change during pregnancy; however, the role of the epigenetic modifier UHRF1 in trophoblast regulation remains unknown. This is the first study to show that UHRF1 expression was localized in the cytoplasm of cytotrophoblasts, syncytiotrophoblasts, and villi columns, and decreased in the villi of patients with RPL. The invasion and cell viability in a UHRF1 knockdown trophoblast cell line were significantly decreased. In addition, the mRNA expression profiles of Swan71 cells were partially altered by UHRF1 knockdown. The altered immune‐related genes were screened out and the pro‐inflammatory TH1‐type chemokine/cytokines CXCL2 and IL‐1β were identified as the most promising targets of UHRF1 in the trophoblasts, which were significantly increased in the UHRF1 knockdown Swan71 cells, villi, and serum from patients with RPL. The macrophages treated with the supernatants of UHRF1 knockdown Swan71 cells were polarized to the M1 phenotype and secreted high levels of pro‐inflammatory cytokines, which might be driven by the activated MyD88/NF‐κB signaling pathway and mediated by the increased expression of CXCR2 and IL‐1R1 (CXCL2 and IL‐1β receptors, respectively). In addition, the supernatants of UHRF1 knockdown Swan71 cells showed stronger chemotaxis to macrophages than those from the controls. Our findings highlight the previously unknown roles of UHRF1 as one of the key regulators on the trophoblasts and their cross‐talk with local immune cells, and demonstrate a potential approach for RPL intervention.

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Polymorphisms in the CIITA −168A/G (rs3087456) and CIITA +1614G/C (rs4774) may influence severity in multiple sclerosis patients

Cited by 7 publications

References 42 publications

HLA-DQA1*04:01 is related to a higher multiple sclerosis lesion load on T2/Flair MRI sequences

HLA-DQA1*04:01 is related to a higher multiple sclerosis lesion load on T2/Flair MRI sequences

Association between variant alleles of major histocompatibility complex class II regulatory genes and nasopharyngeal carcinoma susceptibility

UHRF1 shapes both the trophoblast invasion and decidual macrophage differentiation in early pregnancy

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