School of Public Health, University of Haifa, Haifa, Israel.
Multiple Sclerosis Center, Sheba Medical Center, Ramat Gan, Israel.
PLoS One. 2023 Feb 7;18(2):e0280515. doi: 10.1371/journal.pone.0280515. eCollection 2023.
Although the causes of multiple sclerosis are largely unknown, genetic and environmental components play an important role. Geographic distribution, varying with latitude, reflects both genetic and environmental influences. We conducted a retrospective exploratory observational study to characterize the disability progression of 2396 Jewish patients with relapsing-remitting multiple sclerosis, followed at the Sheba Multiple Sclerosis Center, Tel-Aviv, Israel; 188 patients who originated in Iraq and 2207 patients who originated in northern Europe. Peripheral blood microarray gene expression analysis was performed in a subgroup of patients to identify molecular pathways associated with faster disability progression. During a follow-up period of 18.8 and 19.8 years, respectively, 51.6% of patients with an Iraqi origin progressed to moderate disability defined as expanded disability status scale (EDSS) score of 3.0 to 5.5, compared to 44.2% of patients with a northern European origin (odds ratio 1.347, 95% CI 1.0-1.815, p = 0.049). An Iraqi origin was associated with increased risk of progression to moderate disability adjusted for sex, disease duration, age at onset, and treatment with immunomodulatory drugs (hazard ratio 1.323; 95% CI, 1.049-1.668, p = 0.02), but not to severe disability defined as EDSS score > = 6.0 (i.e., walking aids are required for a distance of 100 meters, (hazard ratio 1.311; 95% CI, 0.918-1.874, p = 0.136). Gene expression analysis disclosed 98 differentially expressed genes (79 over-expressed and 19 under-expressed) between relapsing-remitting multiple sclerosis patients of Iraqi origin (N = 17) and northern European (N = 34) origin. Interestingly, this gene expression was enriched with genes related to neuronal pathways associated with morphology of axons, branching of neurites, proliferation of neocortical neurons, and formation of myelin sheath, suggesting an augmented process of neurodegeneration in relapsing-remitting multiple sclerosis patients with an Iraqi origin. The study results suggest that relapsing-remitting multiple sclerosis patients with an Iraqi origin progress faster to disability possibly due to an enhanced process of neurodegeneration.
虽然多发性硬化症的病因在很大程度上尚不清楚，但遗传和环境因素起着重要作用。地理分布随纬度而变化，反映了遗传和环境的影响。我们对在以色列特拉维夫的希巴多发性硬化症中心接受随访的 2396 名复发性缓解型多发性硬化症的犹太患者的残疾进展情况进行了回顾性探索性观察研究；其中 188 名患者来自伊拉克，2207 名患者来自北欧。对部分患者进行外周血微阵列基因表达分析，以确定与残疾进展较快相关的分子途径。在分别为 18.8 年和 19.8 年的随访期间，与来自北欧的患者相比，51.6%的伊拉克裔患者进展为中度残疾（定义为扩展残疾状况量表[EDSS]评分为 3.0 至 5.5），而来自北欧的患者为 44.2%（比值比 1.347，95%置信区间 1.0-1.815，p = 0.049）。调整性别、疾病持续时间、发病年龄和免疫调节药物治疗后，伊拉克裔患者进展为中度残疾的风险增加（风险比 1.323；95%置信区间 1.049-1.668，p = 0.02），但进展为严重残疾（定义为 EDSS 评分≥6.0，即需要助行器行走 100 米的距离）的风险没有增加（风险比 1.311；95%置信区间 0.918-1.874，p = 0.136）。基因表达分析显示，来自伊拉克（N = 17）和北欧（N = 34）的复发性缓解型多发性硬化症患者之间有 98 个差异表达基因（79 个上调，19 个下调）。有趣的是，这种基因表达与与轴突形态、神经突分支、新皮层神经元增殖和髓鞘形成相关的神经元途径相关的基因富集，提示复发性缓解型多发性硬化症患者中存在增强的神经退行性过程。该研究结果表明，来自伊拉克的复发性缓解型多发性硬化症患者残疾进展更快，可能是由于神经退行性过程增强。
