Hilven Kelly, Patsopoulos Nikolaos A, Dubois Bénédicte, Goris An
Laboratory for Neuroimmunology, Department of Neurosciences, Experimental Neurology, KU Leuven - University of Leuven, Belgium.
Department of Neurology, Brigham & Women's Hospital, USA/Harvard Medical School, USA/Broad Institute, USA.
Mult Scler. 2015 Nov;21(13):1670-80. doi: 10.1177/1352458514568174. Epub 2015 May 6.
More than 100 common variants underlying multiple sclerosis (MS) susceptibility have been identified, but their effect on disease phenotype is still largely unknown.
The objective of this paper is to assess whether the cumulative genetic risk score of currently known susceptibility variants affects clinical presentation.
A cumulative genetic risk score was based on four human leukocyte antigen (HLA) and 106 non-HLA risk loci genotyped or imputed in 842 Belgian MS patients and 321 controls. Non-parametric analyses were applied.
An increased genetic risk is observed for MS patients, including subsets such as oligoclonal band-negative and primary progressive MS patients, compared to controls. Within the patient group, a stronger association between HLA risk variants and the presence of oligoclonal bands, an increased immunoglobulin G (IgG) index and female gender was apparent. Results suggest an association between a higher accumulation of non-HLA risk variants and increased relapse rate as well as shorter relapse-free intervals after disease onset.
MS patients display a significantly increased genetic risk compared to controls, irrespective of disease course or presence of oligoclonal bands. Whereas the cumulative burden of non-HLA risk variants appears to be reflected in the relapses of MS patients, the HLA region influences intrathecal IgG levels.
已鉴定出100多个与多发性硬化症（MS）易感性相关的常见变异，但它们对疾病表型的影响仍大多未知。
本文旨在评估目前已知的易感性变异的累积遗传风险评分是否影响临床表现。
累积遗传风险评分基于对842例比利时MS患者和321例对照进行基因分型或推断的4种人类白细胞抗原（HLA）和106个非HLA风险位点。应用非参数分析。
与对照组相比，MS患者（包括寡克隆带阴性和原发进展型MS患者等亚组）的遗传风险增加。在患者组中，HLA风险变异与寡克隆带的存在、免疫球蛋白G（IgG）指数升高和女性性别之间存在更强的关联。结果表明，非HLA风险变异的更高累积与复发率增加以及疾病发作后无复发间隔时间缩短之间存在关联。
与对照组相比，MS患者的遗传风险显著增加，无论疾病病程或寡克隆带的存在情况如何。虽然非HLA风险变异的累积负担似乎反映在MS患者的复发中，但HLA区域影响鞘内IgG水平。
