AUTHOR=Chen Changying , Gu Xincheng , Liu Fangyuan , Sun Congyong , Mu Jialin , Jin Defu , Sui Xuemei , Geng Deqin , Li Qingqing , Jiang Yuzhang , Shen Chong 

TITLE=SNP rs3803264 polymorphisms in THSD1 and abnormally expressed mRNA are associated with hemorrhagic stroke

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=15

YEAR=2023

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1144364

DOI=10.3389/fnagi.2023.1144364

ISSN=1663-4365

ABSTRACT=<sec><title>Background</title><p>Thrombospondin Type 1 Domain Containing Protein 1 (THSD1) has been suggested to be a new regulator of endothelial barrier function in the angiogenesis process, preserving vascular integrity. We sought to characterize the association of <italic>THSD1</italic> genetic variants and mRNA expression with the risk of hemorrhagic stroke (HS) with population-based evidence.</p></sec><sec><title>Methods</title><p>A case–control study was conducted with 843 HS cases and 1,400 healthy controls. A cohort study enrolled 4,080 participants free of stroke at baseline in 2009 and followed up to 2022. A synonymous variant, the main tag SNP rs3803264 of the <italic>THSD1</italic> gene, was genotyped in all subjects, and peripheral leukocyte <italic>THSD1</italic> mRNA expression was detected using RT-qPCR in 57 HS cases and 119 controls.</p></sec><sec><title>Results</title><p>In the case–control study, rs3803264 AG/GG variations are associated with a decreased risk of HS with odd ratio (<italic>OR</italic>) and 95% confidence interval (<italic>CI</italic>) of the dominant model of 0.788 (0.648–0.958), <italic>p</italic> = 0.017. In addition, rs3803264 and dyslipidemia had a multiplicative interaction [<italic>OR</italic> (95% <italic>CI</italic>) = 1.389 (1.032, 1.869), <italic>p</italic> = 0.030]. In the cohort study, a similar association strength of rs3803264 dominant model and the risk of HS was observed with the incidence rate ratio (<italic>IRR</italic>) of 0.734 and <italic>p</italic>-value of 0.383. Furthermore, the risk of HS showed a non-linear as <italic>THSD1</italic> mRNA expression increased (<italic>p</italic> for non-linearity &lt;0.001). For the subjects without hypertension, we observed <italic>THSD1</italic> mRNA expression had a negative correlation with systolic blood pressure (SBP; <italic>ρ</italic> = −0.334, <italic>p</italic> = 0.022).</p></sec><sec><title>Conclusion</title><p>SNP rs3803264 polymorphisms in <italic>THSD1</italic> are associated with the decreased risk of HS and interacted with dyslipidemia, and a non-linear association was observed between <italic>THSD1</italic> mRNA expression and the risk of HS.</p></sec>