Pereira Valéria Coelho Santa Rita, Fontes-Dantas Fabrícia Lima, Paradela Eduardo Ribeiro, Malfetano Fabíola Rachid, Scherpenhuijzen Simone de Souza Batista, Mansur Letícia Fêzer, Luiz Ronir Raggio, Oliveira André Peres De, Farinhas João Gabriel Dib, Maiolino Ângelo, Alves-Leon Soniza Vieira
Universidade Federal do Rio de Janeiro, Departamento de Neurologia, Rio de Janeiro RJ, Brasil.
Universidade Federal do Estado do Rio de Janeiro, Laboratório de Neurociências Translacional, Programa de Pós-Graduação em Neurologia, Rio de Janeiro RJ, Brasil.
Arq Neuropsiquiatr. 2019 Mar;77(3):166-173. doi: 10.1590/0004-282X20190026.
It is currently unknown how genetic factors may influence the clinical course of multiple sclerosis (MS).
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.
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).
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.
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.
目前尚不清楚遗传因素如何影响多发性硬化症（MS）的临床病程。
我们研究了CIITA基因多态性-168A/G（rs3087456）和+1614G/C（rs4774）对残疾进展风险、疾病严重程度以及一线免疫调节治疗反应的影响。
从血液样本中提取基因组DNA。我们使用ABI3730xl和GeneMapper v.4.0软件来识别基因型变异。所有患者均接受随访，并每三个月进行一次临床重新评估。残疾进展通过扩展残疾状态量表进行测量，疾病严重程度通过多发性硬化症痉挛量表（MSSS）进行测量。
我们纳入了37名男性和80名女性。我们没有发现所研究的单核苷酸多态性对扩展残疾状态量表或所评估药物的治疗反应有影响的证据。我们对MSSS进行了逻辑回归分析，发现病情较轻的MS病程与野生型CIITA -168AA和CIITA +1614GG相关，因为CIITA -168AA患者进展到MSSS2和MSSS3的几率分别降低了61%和75%，CIITA +1614GG患者分别降低了66%和75%（p < 0.0001）。虽然不太显著，但CIITA +1614 GC也表明MS病程较轻，患者进展到MSSS3的几率降低了79%（p = 0.015）。我们还观察到，CIITA -168GG基因型在MSSS2和MSSS3中更常见，病情加重的几率比低40%。
这些数据表明，CIITA -168AA、CIITA +1614GG和CIITA +1614 GC多态性可能与更好的MS临床病程相关。这一知识可能有助于更好地理解MS及其治疗管理。
