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Original article
Serine proteases of the complement lectin pathway and their genetic variations in ischaemic stroke
  1. Gohar Tsakanova1,
  2. Ani Stepanyan1,
  3. Karen Nahapetyan2,
  4. Robert B Sim3,4,
  5. Arsen Arakelyan1,
  6. Anna Boyajyan1
  1. 1 Institute of Molecular Biology NAS RA, Yerevan, Armenia
  2. 2 Department of Neurosurgery, ’Armenia' Republican Medical Center, Yerevan, Armenia
  3. 3 Department of Pharmacology, Oxford University, Oxford, UK
  4. 4 Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK
  1. Correspondence to Dr Gohar Tsakanova, Laboratory of Human Genomics and Immunomics, Institute of Molecular Biology NAS RA, 7 Hasratyan Street, Yerevan 0014, Armenia; g_tsakanova{at}mb.sci.am

Abstract

Aims 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 MASP1 gene and rs2273343, rs12711521, rs147270785 in MASP2 gene) with this pathology.

Methods 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 MASP1 and MASP2 genetic polymorphisms with ischaemic stroke.

Results 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 MASP1 gene and the rs147270785 polymorphism in the MASP2 gene are associated with ischaemic stroke (p<0.0001).

Conclusions 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 MASP1 and MASP2 genes, respectively, are strongly associated with ischaemic stroke, and the minor rs3203210*C and rs147270785*A alleles of these polymorphisms may be considered as protective factors for ischameic stroke, at least in the Armenian population.

  • ischaemic stroke
  • complement lectin pathway serine proteases
  • MASP1
  • MASP2
  • enzyme activity
  • single nucleotide polymorphisms

https://doi.org/10.1136/jclinpath-2017-204403

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    Footnotes

    • Handling editor Tahir S Pillay.

    • Contributors All authors contributed extensively to the work presented in this manuscript. AB and RBS designed and supervised the experiments, AS participated in the performance of experiments and data analysis, KN helped with the analysis of the clinical histories of the patients, AA analysed and interpreted the data, as well as helped to evaluate and edit the manuscript, GT designed the primers, performed the experiments and jointly wrote the manuscript. All authors discussed the results and implications and commented on the manuscript at all stages.

    • Competing interests None declared.

    • Ethics approval Ethical Committee of the Institute of Molecular Biology NAS RA (IRB #00004079).

    • Provenance and peer review Not commissioned; externally peer reviewed.