Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Priority Area Chronic Lung Diseases, Research Center Borstel, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Borstel, Germany.
J Neuroimmunol. 2022 Nov 15;372:577937. doi: 10.1016/j.jneuroim.2022.577937. Epub 2022 Aug 1.
Here we aimed to compare association of common immune-related genetic variants with three autoimmune central nervous system (CNS) demyelinating diseases, namely myelin oligodendrocyte glycoprotein-associated disease (MOGAD), multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD).
In this retrospective cross-sectional study, 26 common immune-related single nucleotide polymorphisms were genotyped in 102 patients with MOGAD, 100 patients with MS, 198 patients with NMOSD and 541 healthy control subjects recruited from Guangzhou, China.
Among all tested genetic variations, one polymorphism, B cell scaffold protein with ankyrin repeats 1 (BANK1) rs4522865 was associated with multiple disorders, namely MOGAD (OR = 1.94, 95% CI:1.19-3.17, P = 0.0059) and NMOSD (OR = 1.69, 95% CI:1.17-2.45). Besides BANK1 rs4522865, two other non-HLA loci, ribonuclease T2 (RNASET2) rs9355610 (OR = 0.47, 95% CI: 0.26-0.85) and TNFAIP3 interacting protein 1 (TNIP1) rs10036748 (OR = 1.76, 95% CI: 1.16-2.71), were associated with MOGAD. In addition, NMOSD was associated with signal transducer and activator of transcription 4 (STAT4) rs7574865 (OR = 1.58, 95% CI: 1.12-2.24) and general transcription factor Iii (GTF2I) rs73366469 (OR = 1.60, 95% CI:1.12-2.29), while MS was associated with a killer cell lectin like receptor G1 (KLRG1) rs1805673 (OR = 0.61, 95% CI: 0.40-0.94) and T-box transcription factor 21 (TBX21) rs17244587 (OR = 2.25, 95% CI: 1.25-4.06).
The current study suggests for the first time three non-HLA susceptibility loci for MOGAD. In addition, comparison of association of 26 immune-related polymorphisms with three autoimmune CNS demyelinating diseases demonstrates substantial difference in genetic basis of those disorders.
本研究旨在比较常见的免疫相关遗传变异与三种自身免疫性中枢神经系统（CNS）脱髓鞘疾病（即髓鞘少突胶质细胞糖蛋白相关疾病（MOGAD）、多发性硬化症（MS）和视神经脊髓炎谱系障碍（NMOSD））之间的关联。
在这项回顾性病例对照研究中，我们在来自中国广州的 102 名 MOGAD 患者、100 名 MS 患者、198 名 NMOSD 患者和 541 名健康对照中检测了 26 个常见的免疫相关单核苷酸多态性。
在所有测试的遗传变异中，一种多态性，B 细胞支架蛋白含有锚蛋白重复序列 1（BANK1）rs4522865 与多种疾病相关，即 MOGAD（OR=1.94，95%CI：1.19-3.17，P=0.0059）和 NMOSD（OR=1.69，95%CI：1.17-2.45）。除了 BANK1 rs4522865 之外，另外两个非 HLA 基因座，核糖核酸酶 T2（RNASET2）rs9355610（OR=0.47，95%CI：0.26-0.85）和肿瘤坏死因子-α诱导蛋白 3 相互作用蛋白 1（TNIP1）rs10036748（OR=1.76，95%CI：1.16-2.71），与 MOGAD 相关。此外，NMOSD 与信号转导和转录激活因子 4（STAT4）rs7574865（OR=1.58，95%CI：1.12-2.24）和一般转录因子 III（GTF2I）rs73366469（OR=1.60，95%CI：1.12-2.29）相关，而 MS 与杀伤细胞凝集素样受体 G1（KLRG1）rs1805673（OR=0.61，95%CI：0.40-0.94）和 T 框转录因子 21（TBX21）rs17244587（OR=2.25，95%CI：1.25-4.06）相关。
本研究首次提出了三个与 MOGAD 相关的非 HLA 易感性基因座。此外，对 26 个免疫相关多态性与三种自身免疫性中枢神经系统脱髓鞘疾病之间的关联进行比较，表明这些疾病的遗传基础存在显著差异。
