Alignment of EGF-like repeat domain of NOTCH3.

<p>Alignment of C4–C6 in EGF-like domains of NOTCH3 was shown in the upper panel (A). Conserved G36 in human EGF is shown in the most EGF-like domains of NOTCH3. Alignment of C4–C6 in EGF-like repeat domain 3 homolog from different species was shown in the middle panel of the figure (B). Amino acid sequence alignment from various species showed the conservation of this glycine residue. The reported CADASIL mutations within this EGF-like repeat domain were indicated in the lower panel (C).</p

Information of primers used in PCR amplification for <i>NOTCH3</i> gene.

<p>Information of primers used in PCR amplification for <i>NOTCH3</i> gene.</p

A novel G149V mutation found in a CADASIL family.

<p>The pedigree of this Chinese CADASIL family was shown (A). The proband is indicated with an arrow. MscI digestion results corresponding to each individual were shown below the pedigree. The affected showed a digested band (131 bp) with an undigested band (149 bp), while the normal controls showed only one digested band at 131 bp. III1 and III3 carried the mutation but are asymptomatic so far. Electropherograms of the sequence showed the nucleotide change in the affected individual with respect to the normal control bp. III1 and III3 carried the mutation but are asymptomatic so far. Electropherograms of the sequence showed the nucleotide change in the affected individual with respect to the normal control (B). P.G149V (c.446G>T) was indicated with an arrow.</p

Brain MRI images of the proband showing characteristic diffuse leukoencephalopathy.

<p>T2-weighted MRI images (A–C) showed diffuse hyperintensities in the periventricular white matter with a symmetrical distribution, the centrum semiovale, and the basal ganglia. Fluid-attenuated inversion recovery (FLAIR) T2 sequences (D–F) revealed confluent white-matter lesions in multiple brain regions. Diffusion-weighted imaging (DWI) sequence (G) demonstrated acute ischemic stroke in the centrum semiovale. MR angiography (H) revealed no intracranial arterial stenosis or occlusion.</p

Data_Sheet_1_SNP rs3803264 polymorphisms in THSD1 and abnormally expressed mRNA are associated with hemorrhagic stroke.docx

BackgroundThrombospondin 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 THSD1 genetic variants and mRNA expression with the risk of hemorrhagic stroke (HS) with population-based evidence.MethodsA 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 THSD1 gene, was genotyped in all subjects, and peripheral leukocyte THSD1 mRNA expression was detected using RT-qPCR in 57 HS cases and 119 controls.ResultsIn the case–control study, rs3803264 AG/GG variations are associated with a decreased risk of HS with odd ratio (OR) and 95% confidence interval (CI) of the dominant model of 0.788 (0.648–0.958), p = 0.017. In addition, rs3803264 and dyslipidemia had a multiplicative interaction [OR (95% CI) = 1.389 (1.032, 1.869), p = 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 (IRR) of 0.734 and p-value of 0.383. Furthermore, the risk of HS showed a non-linear as THSD1 mRNA expression increased (p for non-linearity ConclusionSNP rs3803264 polymorphisms in THSD1 are associated with the decreased risk of HS and interacted with dyslipidemia, and a non-linear association was observed between THSD1 mRNA expression and the risk of HS.</p

Image_1_SNP rs3803264 polymorphisms in THSD1 and abnormally expressed mRNA are associated with hemorrhagic stroke.PDF

BackgroundThrombospondin 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 THSD1 genetic variants and mRNA expression with the risk of hemorrhagic stroke (HS) with population-based evidence.MethodsA 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 THSD1 gene, was genotyped in all subjects, and peripheral leukocyte THSD1 mRNA expression was detected using RT-qPCR in 57 HS cases and 119 controls.ResultsIn the case–control study, rs3803264 AG/GG variations are associated with a decreased risk of HS with odd ratio (OR) and 95% confidence interval (CI) of the dominant model of 0.788 (0.648–0.958), p = 0.017. In addition, rs3803264 and dyslipidemia had a multiplicative interaction [OR (95% CI) = 1.389 (1.032, 1.869), p = 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 (IRR) of 0.734 and p-value of 0.383. Furthermore, the risk of HS showed a non-linear as THSD1 mRNA expression increased (p for non-linearity ConclusionSNP rs3803264 polymorphisms in THSD1 are associated with the decreased risk of HS and interacted with dyslipidemia, and a non-linear association was observed between THSD1 mRNA expression and the risk of HS.</p