Tsakanova Gohar, Stepanyan Ani, Nahapetyan Karen, Sim Robert B, Arakelyan Arsen, Boyajyan Anna
Institute of Molecular Biology NAS RA, Yerevan, Armenia.
Department of Neurosurgery, 'Armenia' Republican Medical Center, Yerevan, Armenia.
J Clin Pathol. 2018 Feb;71(2):141-147. doi: 10.1136/jclinpath-2017-204403. Epub 2017 Jul 18.
The aim of the current study was to assess the proteolytic activities of collectin-bound MASP-1 and MASP-2 in the blood of patients with ischaemic stroke, as well as the association of their six genetic polymorphisms (rs3203210, rs28945070, rs28945073 in gene and rs2273343, rs12711521, rs147270785 in gene) with this pathology.
In total, 250 patients and 300 healthy subjects were involved in this study. MBL-associated serine protease (MASP)-1 and MASP-2 activities were measured using in-house developed immunofluorescent and enzyme-linked immunosorbent assays, respectively. Sequence specific primer PCR was used to study the association of and genetic polymorphisms with ischaemic stroke.
The results obtained demonstrate that the activities of collectin-bound MASP-1 and MASP-2 in patients with ischaemic stroke are significantly higher than those in healthy subjects (p<0.001). According to the data obtained for genotyping, the rs3203210 polymorphism in the gene and the rs147270785 polymorphism in the gene are associated with ischaemic stroke (p<0.0001).
In conclusion we suggest that the complement lectin pathway serine proteases, MASP-1 and MASP-2, can be associated with ischaemic stroke development risk and may participate in pathological events leading to post-ischaemic brain damage. Moreover rs3203210 and rs147270785 single nucleotide polymorphisms in the and genes, respectively, are strongly associated with ischaemic stroke, and the minor rs3203210C and rs147270785A alleles of these polymorphisms may be considered as protective factors for ischameic stroke, at least in the Armenian population.
本研究旨在评估缺血性中风患者血液中结合凝集素的甘露聚糖结合凝集素相关丝氨酸蛋白酶-1（MASP-1）和甘露聚糖结合凝集素相关丝氨酸蛋白酶-2（MASP-2）的蛋白水解活性，以及它们的六个基因多态性（MASP1基因中的rs3203210、rs28945070、rs28945073和MASP2基因中的rs2273343、rs12711521、rs147270785）与该疾病的关联。
本研究共纳入250例患者和300名健康受试者。分别使用自行开发的免疫荧光法和酶联免疫吸附测定法测量MBL相关丝氨酸蛋白酶（MASP）-1和MASP-2的活性。采用序列特异性引物PCR研究MASP1和MASP2基因多态性与缺血性中风的关联。
所得结果表明，缺血性中风患者中结合凝集素的MASP-1和MASP-2的活性显著高于健康受试者（p<0.001）。根据基因分型数据，MASP1基因中的rs3203210多态性和MASP2基因中的rs147270785多态性与缺血性中风相关（p<0.0001）。
总之，我们认为补体凝集素途径丝氨酸蛋白酶MASP-1和MASP-2可能与缺血性中风的发病风险相关，并可能参与导致缺血性脑损伤的病理过程。此外，MASP1和MASP2基因中的rs3203210和rs147270785单核苷酸多态性分别与缺血性中风密切相关，这些多态性的次要等位基因rs3203210C和rs147270785A至少在亚美尼亚人群中可被视为缺血性中风的保护因素。
