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

Abstract

BackgroundThrombospondin-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 THBS1 with ischemic stroke (IS) warrants further validation with population-based evidence.ObjectiveTo evaluate the association of single nucleotide polymorphisms (SNPs) and mRNA expression of THBS1 with the risks of IS and long-term death after stroke.MethodsA 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 THBS1 gene, rs2236471 and rs3743125, were genotyped in all subjects and THBS1 mRNA expression of peripheral leukocyte was measured using RT-qPCR in 314 IS cases and 314 controls.ResultsThere is no significant difference in genotype and haplotype frequencies of rs2236741 and rs3743125 between IS cases and controls (all P > 0.05). Furthermore, the cohort studies did not observe significant associations between THBS1 variants and the risk of IS incidence or long-term death after IS (all P > 0.05). The THBS1 mRNA expression level (2–ΔΔCT) in IS cases was approximately equal to that in controls (1.01 vs. 0.99, P = 0.833). In addition, THBS1 mRNA expression had no significant association with all-cause death, stroke death, and IS death of IS patients (all P > 0.05).ConclusionTherefore, our study suggested that there is no significant association of THBS1 polymorphisms and mRNA expression level with the risk of IS and long-term death after IS.

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

“…The methods and reagents of white blood cell separation and preservation, RNA extraction, reverse transcription, and quantitative real-time polymerase chain reaction (RT-qPCR) were consistent with the previous study (Chen et al, 2022). All samples were analyzed in three parallels, and cycle threshold values were recorded.…”

“…Dyslipidemia was defined as definite dyslipidemia history, or abnormal changes in lipid levels (TC ≥ 6.2 mmol/L, TG ≥ 2.3 mmol/L, LDL-C ≥ 4.1 mmol/L, HDL-C < 1.04 mmol/L), or under lipid-modulating therapy. The details of blood sample collection and the methods of biochemical index detection were described previously ( Chen et al, 2022 ).…”

“…The details of DNA extraction and preservation and genotyping were described previously ( Chen et al, 2022 ). The polymerase chain reaction (PCR)-TaqMan MGB probe array was performed for the genotyping of THSD1 polymorphism.…”

Multicenter Validation of lncRNA and Target mRNA Diagnostic and Prognostic Biomarkers of Acute Ischemic Stroke From Peripheral Blood Leukocytes

“…The severity of AIS cases was defined as follows: NIHSS scores (mild, 0–5; moderate, 6–13; severe, 14–40) 25 , 26 , 27 or mRS scores (favorable, mRS ≤2; unfavorable, mRS>2). 28 Long‐term outcomes of AIS cases including death and stroke death were recorded through the local chronic disease and death registration system, using the International Classification of Diseases , Tenth Revision ( ICD‐10 ), which were verified by investigators to ensure data authenticity.…”