Pawlak-Adamska Edyta, Nowak Oskar, Karabon Lidia, Pokryszko-Dragan Anna, Partyka Anna, Tomkiewicz Anna, Ptaszkowski Jakub, Frydecka Irena, Podemski Ryszard, Dybko Jaroslaw, Bilinska Malgorzata
Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigl 12, 53-114 Wroclaw, Poland.
Department of Human Evolutionary Biology, Institute of Anthropology, Adam Mickiewicz University, Umultowska 89, 61-614 Poznan, Poland.
J Neuroimmunol. 2017 Apr 15;305:115-127. doi: 10.1016/j.jneuroim.2017.02.006. Epub 2017 Feb 9.
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), where inflammation, demyelination together with the axonopathy are the cardinal features on pathologic ground, with a combined genetic and environmental background. The associations of PD-1 single nucleotide polymorphisms (SNPs): PD-1.3 (in intron 4), PD-1.5 and PD-1.9 (both in exon 5) with clinical manifestation of MS in 479 south Polish individuals including 203 MS patients were analyzed. Presence of PD-1.5T allele was linked with the first manifestations of disease: diplopia and pyramidal signs - favored pyramidal signs but protected against of diplopia development. Farther, PD-1.3G/PD-1.5C/PD-1.9C haplotype significantly favored whereas GTC protected against diplopia. Besides, GTT haplotype strongly favored non-severe RRMS outcome and ATC haplotype was specific only for these MS patients. Our population-based case-control study, investigating selected three PD-1 SNPs: PD-1.3, PD-1.5 and PD-1.9, revealed that polymorphic variation may be rather disease-modifying than MS risk factor.
多发性硬化症（MS）是一种中枢神经系统（CNS）的炎症性疾病，炎症、脱髓鞘以及轴索性病变是其病理基础的主要特征，具有遗传和环境双重背景。对479名波兰南部个体（包括203名MS患者）中PD-1单核苷酸多态性（SNP）：PD-1.3（位于内含子4）、PD-1.5和PD-1.9（均位于外显子5）与MS临床表现的相关性进行了分析。PD-1.5T等位基因的存在与疾病的首发表现相关：复视和锥体束征——更易出现锥体束征，但可预防复视的发生。此外，PD-1.3G/PD-1.5C/PD-1.9C单倍型显著增加复视风险，而GTC单倍型则可预防复视。此外，GTT单倍型强烈增加非严重复发缓解型多发性硬化症（RRMS）的发病风险，而ATC单倍型仅在这些MS患者中出现。我们基于人群的病例对照研究，调查了选定的三个PD-1 SNP：PD-1.3、PD-1.5和PD-1.9，结果显示多态性变异可能更多是疾病修饰因素而非MS的危险因素。
