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CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2019; 77(03): 166-173
DOI: 10.1590/0004-282X20190026
Article

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

Os polimorfismos no gene CIITA −168A/G (rs3087456) e CIITA +1614G/C (rs4774) podem influenciar a gravidade em pacientes com esclerose múltipla
Valéria Coelho Santa Rita Pereira 
1   Universidade Federal do Rio de Janeiro, Departamento de Neurologia, Rio de Janeiro RJ, Brasil
,
Fabrícia Lima Fontes-Dantas 
2   Universidade Federal do Estado do Rio de Janeiro, Laboratório de Neurociências Translacional, Programa de Pós-Graduação em Neurologia, Rio de Janeiro RJ, Brasil
,
Eduardo Ribeiro Paradela 
2   Universidade Federal do Estado do Rio de Janeiro, Laboratório de Neurociências Translacional, Programa de Pós-Graduação em Neurologia, Rio de Janeiro RJ, Brasil
,
Fabíola Rachid Malfetano 
1   Universidade Federal do Rio de Janeiro, Departamento de Neurologia, Rio de Janeiro RJ, Brasil
,
Simone de Souza Batista Scherpenhuijzen 
1   Universidade Federal do Rio de Janeiro, Departamento de Neurologia, Rio de Janeiro RJ, Brasil
,
Letícia Fêzer Mansur 
2   Universidade Federal do Estado do Rio de Janeiro, Laboratório de Neurociências Translacional, Programa de Pós-Graduação em Neurologia, Rio de Janeiro RJ, Brasil
,
Ronir Raggio Luiz 
1   Universidade Federal do Rio de Janeiro, Departamento de Neurologia, Rio de Janeiro RJ, Brasil
,
André Peres De Oliveira 
2   Universidade Federal do Estado do Rio de Janeiro, Laboratório de Neurociências Translacional, Programa de Pós-Graduação em Neurologia, Rio de Janeiro RJ, Brasil
,
João Gabriel Dib Farinhas 
2   Universidade Federal do Estado do Rio de Janeiro, Laboratório de Neurociências Translacional, Programa de Pós-Graduação em Neurologia, Rio de Janeiro RJ, Brasil
,
Ângelo Maiolino 
1   Universidade Federal do Rio de Janeiro, Departamento de Neurologia, Rio de Janeiro RJ, Brasil
,
Soniza Vieira Alves-Leon 
1   Universidade Federal do Rio de Janeiro, Departamento de Neurologia, Rio de Janeiro RJ, Brasil
2   Universidade Federal do Estado do Rio de Janeiro, Laboratório de Neurociências Translacional, Programa de Pós-Graduação em Neurologia, Rio de Janeiro RJ, Brasil
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ABSTRACT

It is currently unknown how genetic factors may influence the clinical course of multiple sclerosis (MS).

Objective: We examined the impact of CIITA polymorphisms −168A/G (rs3087456) and +1614G/C (rs4774) on the risk of disability progression, severity and on responses to first-line immunomodulator treatments.

Methods: Genomic DNA was extracted from blood samples. We used ABI3730xl and GeneMapper v.4.0 software to identify genotype variations. All patients were followed up and clinically reassessed at three-month intervals. Disability progression was measured by the Expanded Disability Status Scale and disease severity by the Multiple Sclerosis Spasticity Scale (MSSS).

Results: We included 37 men and 80 women. We found no evidence regarding the influence of the single nucleotide polymorphisms studied in the Expanded Disability Status Scale or therapeutic response of the evaluated drugs. We performed a logistic regression analysis with the MSSS and found that a less severe MS course was associated with wild type CIITA −168AA and CIITA +1614GG, as the chance of the patient progressing to MSSS2 and MSSS3 decreased in 61% and 75% with CIITA −168AA and 66% and 75% with CIITA +1614GG, respectively (p < 0.0001). Although less significant, the CIITA +1614 GC also pointed to a less severe MS course and the chance of the patient progressing to MSSS3 decreased 79% (p = 0.015). We also observed that the CIITA −168GG genotype was more frequent in MSSS2 and MSSS3 and had 40% lower odds ratio to becoming more severe MS.

Conclusion: These data suggest that CIITA −168AA, CIITA +1614GG and CIITA +1614 GC polymorphisms may be associated with a better MS clinical course. This knowledge may be useful for a better understanding of MS and its therapeutic management.

RESUMO

Atualmente não se sabe como os fatores genéticos podem influenciar o curso clínico da esclerose múltipla (EM).

Objetivo: Examinamos o impacto dos polimorfismos CIITA −168A/G (rs3087456) e CIITA +1614G/C (rs4774) no risco de progressão da incapacidade, gravidade e resposta aos tratamentos imunomoduladores de primeira linha.

Métodos: O DNA gençmico foi extraído de amostras de sangue. Utilizamos o software ABI3730xl e GeneMapper v.4.0 (Applied Biosystems) para identificar variações genotípicas. Todos os pacientes foram acompanhados e reavaliados clinicamente em intervalos de três meses. A progressão da incapacidade foi medida pela EDSS e a gravidade da doença pelo MSSS.

Resultados: Incluímos 37 homens e 80 mulheres. Não encontramos evidências sobre a influência dos SNPs estudados no EDSS e na resposta terapêutica aos fármacos avaliados. Realizamos uma análise de regressão logística com o MSSS e observamos uma evolução menos grave da EM associada aos tipos selvagens CIITA −168AA e CIITA +1614GG, pois a chance do paciente atingir MSSS2 e MSSS3 diminuiu em 61%/75%, e 66/75% respectivamente (p < 0,0001). Embora menos significativo, o CIITA +1614GC também foi relacionado com evolução menos grave da EM e a chance do paciente atingir o MSSS3 diminuiu 79% (p = 0,015). Nós também observamos que o genótipo CIITA −168GG foi mais frequente no MSSS2 e MSSS3 e teve uma razão de chance 40% menor para atingir forma mais grave da EM.

Conclusão: Estes dados sugerem que os polimorfismos CIITA −168AA, CIITA +1614GG e CIITA +1614GC podem estar associados a um melhor curso clínico da EM. Este conhecimento pode ser útil para uma melhor compreensão da EM e o seu manejo terapêutico.

Keywords:

Multiple sclerosis - Polymorphism, Genetic - Therapeutics - Disease progression

Palavras-chave:

Esclerose múltipla - Polimorfismo genético - Terapêutca - Progressão da doença

Support

This study was funded by support from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-Brazil), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-Brazil).




Publication History

Received: 25 June 2018

Accepted: 29 November 2018

Article published online:
21 August 2023

© 2023. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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