Tsakanova Gohar, Stepanyan Ani, Steffensen Rudi, Soghoyan Armine, Jensenius Jens Christian, Arakelyan Arsen
Institute of Molecular Biology NAS RA, Yerevan, Armenia.
CANDLE Synchrotron Research Institute, Yerevan, Armenia.
Pharmgenomics Pers Med. 2021 Oct 21;14:1347-1368. doi: 10.2147/PGPM.S326242. eCollection 2021.
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 rs12780112T and rs10120023T 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.
本研究旨在调查亚美尼亚人群中缺血性卒中（IS）患者血浆中凝集素补体途径（LCP）的模式识别分子（PRM）、甘露聚糖结合凝集素（MBL）和M-纤维胶凝蛋白的水平，以及MBL和Ficolin基因中11个单核苷酸多态性（SNP）的可能关联。
本研究共纳入122例IS患者和150例对照者。进行了免疫荧光测定法（TRIFMAs）和使用TaqMan探针的实时聚合酶链反应。
结果显示，IS患者的M-纤维胶凝蛋白水平显著高于对照者，MBL基因的rs11003125和rs12780112 SNP，以及Ficolin基因的rs12780112T和rs10120023T次要等位基因（MA）与IS风险呈负相关。此外，MBL基因的rs11003125和rs1800450 SNP及其MA的携带，以及Ficolin基因的rs2989727 SNP和rs10120023*T MA的携带分别显著改变了IS患者的血浆MBL和M-纤维胶凝蛋白水平。揭示了MBL基因中的5种常见单倍型以及MBL和Ficolin基因中的3种常见单倍型，其中CGTC与IS呈负相关，并降低了IS患者的血浆MBL水平。
总之，我们认为LCP PRM与IS的发生风险相关，也可能参与导致缺血性脑损伤的病理过程。本研究强调了LCP PRM在基因组和蛋白质组水平的改变对缺血性卒中发病机制的重要贡献，至少在亚美尼亚人群中如此。
