AUTHOR=Chen Changying , Chen Xuemei , Yang Siyuan , Li Qingqing , Ren Zhanyun , Wang Lu , Jiang Yuzhang , Gu Xincheng , Liu Fangyuan , Mu Jialing , Liu Lihua , Wang Yi , Li Junrong , Yu Yanhua , Zhang Jun , Shen Chong 

TITLE=Association of THBS1 genetic variants and mRNA expression with the risks of ischemic stroke and long-term death after stroke

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=14

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.1006473

DOI=10.3389/fnagi.2022.1006473

ISSN=1663-4365

ABSTRACT=<sec><title>Background</title><p>Thrombospondin-1 (THBS1) derived from platelets and acted as a critical mediator of hemostasis promoting platelet activation in thrombus formation. The biological connection of genetic variants and mRNA expression of <italic>THBS1</italic> with ischemic stroke (IS) warrants further validation with population-based evidence.</p></sec><sec><title>Objective</title><p>To evaluate the association of single nucleotide polymorphisms (SNPs) and mRNA expression of <italic>THBS1</italic> with the risks of IS and long-term death after stroke.</p></sec><sec><title>Methods</title><p>A case-control study consisted of 4,584 IS patients recruited from five hospitals in Jiangsu, China, and 4,663 age-gender-matched controls free of IS. A cohort study enrolled 4,098 participants free of stroke and lasted from 2009 to 2022. Early collected 3158 IS patients aged between 35 and 80 years were followed up an average of 5.86-year to follow up their long-term death outcomes. Two tagSNPs of the <italic>THBS1</italic> gene, rs2236471 and rs3743125, were genotyped in all subjects and <italic>THBS1</italic> mRNA expression of peripheral leukocyte was measured using RT-qPCR in 314 IS cases and 314 controls.</p></sec><sec><title>Results</title><p>There is no significant difference in genotype and haplotype frequencies of rs2236741 and rs3743125 between IS cases and controls (all <italic>P</italic> &gt; 0.05). Furthermore, the cohort studies did not observe significant associations between <italic>THBS1</italic> variants and the risk of IS incidence or long-term death after IS (all <italic>P</italic> &gt; 0.05). The <italic>THBS1</italic> mRNA expression level (2<sup>–Δ</sup><sup>Δ</sup><italic><sup>CT</sup></italic>) in IS cases was approximately equal to that in controls (1.01 vs. 0.99, <italic>P</italic> = 0.833). In addition, <italic>THBS1</italic> mRNA expression had no significant association with all-cause death, stroke death, and IS death of IS patients (all <italic>P</italic> &gt; 0.05).</p></sec><sec><title>Conclusion</title><p>Therefore, our study suggested that there is no significant association of <italic>THBS1</italic> polymorphisms and mRNA expression level with the risk of IS and long-term death after IS.</p></sec>