Department of Neurology and Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany; Department of Neurology, Bern University Hospital, University of Bern, Bern, Switzerland.
Mult Scler. 2019 Apr;25(5):661-668. doi: 10.1177/1352458518763541. Epub 2018 Mar 13.
The course of multiple sclerosis (MS) shows substantial inter-individual variability. The underlying determinants of disease severity likely involve genetic and environmental factors.
The aim of this study was to assess the impact of APOE and HLA polymorphisms as well as smoking and body mass index (BMI) in the very early MS course.
Untreated patients ( n = 263) with a recent diagnosis of relapsing-remitting (RR) MS or clinically isolated syndrome underwent standardized magnetic resonance imaging (MRI). Genotyping was performed for single-nucleotide polymorphisms (SNPs) rs3135388 tagging the HLA-DRB1*15:01 haplotype and rs7412 (Ɛ2) and rs429358 (Ɛ4) in APOE. Linear regression analyses were applied based on the three SNPs, smoking and BMI as exposures and MRI surrogate markers for disease severity as outcomes.
Current smoking was associated with reduced gray matter fraction, lower brain parenchymal fraction and increased cerebrospinal fluid fraction in comparison to non-smoking, whereas no effect was observed on white matter fraction. BMI and the SNPs in HLA and APOE were not associated with structural MRI parameters.
Smoking may have an unfavorable effect on the gray matter fraction as a potential measure of MS severity already in early MS. These findings may impact patients' counseling upon initial diagnosis of MS.
多发性硬化症（MS）的病程表现出显著的个体间差异。疾病严重程度的潜在决定因素可能涉及遗传和环境因素。
本研究旨在评估 APOE 和 HLA 多态性以及吸烟和体重指数（BMI）在 MS 早期病程中的影响。
对未经治疗的近期诊断为复发缓解型（RR）MS 或临床孤立综合征的患者（n=263）进行了标准化的磁共振成像（MRI）检查。对单核苷酸多态性（SNP）rs3135388 进行基因分型，该 SNP 可标记 HLA-DRB1*15:01 单倍型，以及 APOE 中的 rs7412（Ɛ2）和 rs429358（Ɛ4）。基于三个 SNP、吸烟和 BMI 作为暴露因素，以及 MRI 替代标记物作为疾病严重程度的结果，应用线性回归分析。
与不吸烟相比，当前吸烟与灰质分数降低、脑实质分数降低和脑脊液分数增加有关，而与白质分数无关。BMI 和 HLA 及 APOE 中的 SNP 与结构 MRI 参数无关。
吸烟可能对灰质分数产生不利影响，作为 MS 严重程度的潜在衡量标准，即使在 MS 早期也是如此。这些发现可能会影响患者在 MS 初始诊断时的咨询。
