Pharmacogenomics and Personalized Medicine (Oct 2021)

Pattern Recognition Molecules of Lectin Complement Pathway in Ischemic Stroke

  • Tsakanova G,
  • Stepanyan A,
  • Steffensen R,
  • Soghoyan A,
  • Jensenius JC,
  • Arakelyan A

Journal volume & issue
Vol. Volume 14
pp. 1347 – 1368

Abstract

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Gohar Tsakanova,1,2 Ani Stepanyan,1 Rudi Steffensen,3 Armine Soghoyan,4 Jens Christian Jensenius,5 Arsen Arakelyan1 1Institute of Molecular Biology NAS RA, Yerevan, Armenia; 2CANDLE Synchrotron Research Institute, Yerevan, Armenia; 3Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark; 4“Surb Grigor Lusavorich” Medical Center CJSC, Yerevan, Armenia; 5Department of Biomedicine, Aarhus University, Aarhus, DenmarkCorrespondence: Gohar TsakanovaInstitute of Molecular Biology NAS RA, 7 Hasratyan Street, Yerevan, 0014, ArmeniaTel +374 94 123070Fax +374 10 282061Email [email protected]: The current study aimed to investigate in an Armenian population the levels of pattern recognition molecules (PRMs) of lectin complement pathway (LCP), MBL (mannan-binding lectin) and M-ficolin in plasma in ischemic stroke (IS), and the possible association of 11 single nucleotide polymorphisms (SNPs) in MBL2, FCN1 and FCN2 genes.Patients and Methods: A total of 122 patients with IS and 150 control subjects were included in this study. Immunofluorometric assays (TRIFMAs) and real-time polymerase chain reactions with TaqMan probes were conducted.Results: According to the results, the levels of M-ficolin in IS patients are significantly higher than in control subjects, and the MBL2 rs11003125 and rs12780112 SNPs, as well as MBL2 rs12780112*T and FCN1 rs10120023*T minor alleles (MAs) are negatively associated with the risk of IS. Further, MBL2 rs11003125 and rs1800450 SNPs and the carriage of their MAs, as well as FCN1 rs2989727 SNP and the carriage of FCN1 rs10120023*T MA significantly alter plasma MBL and M-ficolin levels in IS patients, respectively. Five common haplotypes in MBL2 gene and three common haplotypes in FCN1 and FCN2 genes were revealed, among which CGTC was negatively associated with IS and decreasing MBL plasma levels in IS.Conclusion: In conclusion, we suggest that LCP PRMs are associated with the risk of developing IS, and may also participate in pathological events leading to post-ischemic brain damage. This study emphasizes the important contribution of alterations of LCP PRMs on genomic and proteomic levels to the pathomechanisms of ischemic stroke, at least in an Armenian population.Keywords: human ischemic stroke, humoral pattern recognition molecules, lectin complement pathway, single nucleotide polymorphisms, haplotypes

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