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

ABSTRACT 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.

摘要 研究背景：多发性硬化（multiple sclerosis, MS）的遗传易感性与人类白细胞抗原（human leukocyte antigen, HLA）等位基因相关，尤其是HLA-DRB1*15:01。研究目的：旨在明确巴西多发性硬化患者队列中磁共振成像（magnetic resonance imaging, MRI）表现与遗传学特征之间的关联。研究方法：本研究回顾性分析了95例连续性多发性硬化患者的临床资料。两名对临床数据设盲的独立观察者对T1加权MRI序列中的空洞病灶进行识别，并对T2加权及液体衰减反转恢复（fluid attenuation inversion recovery, FLAIR）序列中的对比强化病灶进行计数与测量。研究对象按病灶大小、数量及体积进行分组。采用美国加利福尼亚州卡诺加帕克市One Lambda公司试剂盒，通过序列特异性引物聚合酶链反应（polymerase chain reaction, PCR）对HLA-DRB1、HLA-DQB1及HLA-DQA1等位基因，以及rs4774、rs3087456、rs6897932、rs731236和rs1033182单核苷酸多态性位点进行分型鉴定。研究结果：携带HLA-DQA1*04:01等位基因的患者，其病灶负荷（校正年龄、性别及病程后）高于其他HLA-DQA1等位基因携带者（p=0.02）。其余所有HLA等位基因及单核苷酸多态性位点与病灶负荷均无显著差异。研究结论：HLA-DQA1*04:01等位基因与T2/FLAIR MRI序列上更高的病灶负荷相关，提示该等位基因的存在与多发性硬化病情更严重的风险相关。