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CC BY 4.0 · Arq Neuropsiquiatr 2024; 82(S 01): S1-S52
DOI: 10.1055/s-0044-1789375
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FCGR2A rs1801274 polymorphism is associated with response to natalizumab in multiple sclerosis patients

Matheus D. de Matos
1   Universidade do Estado do Rio de Janeiro, Departamento de Farmacologia e Psicobiologia, Laboratório de Neurobiologia do Desenvolvimento, Rio de Janeiro RJ, Brazil.
,
Rafaella C. Cardoso
2   Universidade do Estado do Rio de Janeiro, Rio de Janeiro RJ, Brazil.
,
Larissa A. Duarte
3   Universidade Federal do Estado do Rio de Janeiro, Laboratório de Neurociência Translacional, Rio de Janeiro RJ, Brazil.
,
Barbara D. Guimenez
1   Universidade do Estado do Rio de Janeiro, Departamento de Farmacologia e Psicobiologia, Laboratório de Neurobiologia do Desenvolvimento, Rio de Janeiro RJ, Brazil.
,
Giovanni K. Pavani
1   Universidade do Estado do Rio de Janeiro, Departamento de Farmacologia e Psicobiologia, Laboratório de Neurobiologia do Desenvolvimento, Rio de Janeiro RJ, Brazil.
,
Kamilla A. Fernandez
4   Universidade do Estado do Rio de Janeiro, Hospital Universitário Pedro Ernesto, Serviço de Neurologia, Rio de Janeiro RJ, Brazil.
,
João Gabriel Dib Farinhas
5   Instituto de Ensino e Pesquisa Americas, Rio de Janeiro RJ, Brazil.
,
Felipe da R. Schmidt
4   Universidade do Estado do Rio de Janeiro, Hospital Universitário Pedro Ernesto, Serviço de Neurologia, Rio de Janeiro RJ, Brazil.
,
Guillherme C. Montes
1   Universidade do Estado do Rio de Janeiro, Departamento de Farmacologia e Psicobiologia, Laboratório de Neurobiologia do Desenvolvimento, Rio de Janeiro RJ, Brazil.
,
Soniza V. Alves-Leon
3   Universidade Federal do Estado do Rio de Janeiro, Laboratório de Neurociência Translacional, Rio de Janeiro RJ, Brazil.
,
Fabricia L. Fontes-Dantas
1   Universidade do Estado do Rio de Janeiro, Departamento de Farmacologia e Psicobiologia, Laboratório de Neurobiologia do Desenvolvimento, Rio de Janeiro RJ, Brazil.
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    Address for correspondence: João Gabriel Dib Farinhas (email: jgabrieldib@gmail.com).

    Abstract

    Multiple sclerosis (MS) is recognized as the most prevalent autoimmune disorder affecting the central nervous system (CNS). Natalizumab (NTZ) is among the commonly-used high-efficacy treatments, showing efficacy in reducing MS activity and progression in most patients. It acts by targeting α-4 integrin subunits on lymphocytes, which is crucial to facilitate leukocyte trafficking to sites of inflammation. Several environmental or genetic factors can influence MS treatment success. Currently, there are few established pharmacogenetic predictors of response to treatment in MS patients. One genetic variant associated with therapeutic response to the monoclonal antibodies used in the treatment is the single nucleotide polymorphism (SNP) rs1801274 in the FCGR2A gene. Therefore, the objective of the present study is to assess whether this genetic variant can serve as a potential predictor of therapeutic failure in NTZ treatment for MS. A total of 104 blood samples were collected from patients admitted to 2 university hospitals in Rio de Janeiro, with approval from the Ethics Committee (CAAE:5,782,087). Genomic DNA was extracted from leukocytes for subsequent use in real-time PCR genotyping. Among the patients, nine exhibited confirmed therapeutic failure to NTZ treatment. Following statistical analysis, a significant association was identified between the GG genotype of FCGR2A (p = 0.0004; OR = 0.3530) and therapeutic failure. Additionally, a higher frequency of the AG genotype was observed in patients who did not experience therapeutic failure (p = 0.0002; OR = 3.144). Previous research has posited that FCgRs may also impact the efficacy and tolerability of human monoclonal antibody strategies targeting anti-α-4 integrin. Given the genetic diversity of the Brazilian population due to miscegenation, our preliminary findings suggest the necessity to investigate the role of FCGR2A rs1801274 as a potential pharmacogenetic predictor for MS patients’ response to NTZ.


     

    Die Autoren geben an, dass kein Interessenkonflikt besteht.

    Publikationsverlauf

    Artikel online veröffentlicht:
    02. Oktober 2024

    © 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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