Pattern Recognition Molecules of Lectin Complement Pathway in Ischemic Stroke

• Published in: Pharmacogenomics and personalized medicine Vol. 14; pp. 1347 - 1368
• Main Authors: Tsakanova, Gohar, Stepanyan, Ani, Steffensen, Rudi, Soghoyan, Armine, Jensenius, Jens Christian, Arakelyan, Arsen
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2021; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: Antibodies; Binding sites; Blood & organ donations; Brain damage; Brain injury; Chromosomes; DNA probes; Ethylenediaminetetraacetic acid; Genes; Genetic aspects; Haplotypes; human ischemic stroke; humoral pattern recognition molecules; Ischemia; lectin complement pathway; Lectins; M-ficolin; Mannan; Mannose-binding lectin; Original Research; Pattern recognition; Plasma; Plasma levels; Polymerase chain reaction; Population; Proteins; Proteomics; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Stroke; Stroke (Disease); Armenia; United States > US; humoral pattern recognition molecules; haplotypes; human ischemic stroke; single nucleotide polymorphisms; lectin complement pathway
• ISSN: 1178-7066; 1178-7066
• DOI: 10.2147/PGPM.S326242

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 and genes. 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 probes were conducted. According to the results, the levels of M-ficolin in IS patients are significantly higher than in control subjects, and the rs11003125 and rs12780112 SNPs, as well as rs12780112*T and rs10120023*T minor alleles (MAs) are negatively associated with the risk of IS. Further, rs11003125 and rs1800450 SNPs and the carriage of their MAs, as well as rs2989727 SNP and the carriage of rs10120023*T MA significantly alter plasma MBL and M-ficolin levels in IS patients, respectively. Five common haplotypes in gene and three common haplotypes in and genes were revealed, among which CGTC was negatively associated with IS and decreasing MBL plasma levels in IS. 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.