Genetic Markers for Thrombophilia and Cardiovascular Disease Associated with Multiple Sclerosis
Open Access
- 21 October 2022
- journal article
- research article
- Published by MDPI AG in Biomedicines
- Vol. 10 (10), 2665
- https://doi.org/10.3390/biomedicines10102665
Abstract
Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) with an unknown etiology, although genetic, epigenetic, and environmental factors are thought to play a role. Recently, coagulation components have been shown to provide immunomodulatory and pro-inflammatory effects in the CNS, leading to neuroinflammation and neurodegeneration. The current study aimed to determine whether patients with MS exhibited an overrepresentation of polymorphisms implicated in the coagulation and whether such polymorphisms are associated with advanced disability and disease progression. The cardiovascular disease (CVD) strip assay was applied to 48 MS patients and 25 controls to analyze 11 genetic polymorphisms associated with thrombosis and CVD. According to our results, FXIIIVal34Leu heterozygosity was less frequent (OR: 0.35 (95% CI: 0.12–0.99); p = 0.04), whereas PAI-1 5G/5G homozygosity was more frequent in MS (OR: 6.33 (95% CI: 1.32–30.24); p = 0.016). In addition, carriers of the HPA-1a/1b were likely to have advanced disability (OR: 1.47 (95% CI: 1.03–2.18); p = 0.03) and disease worsening (OR: 1.42 (95% CI: 1.05–2.01); p = 0.02). The results of a sex-based analysis revealed that male HPA-1a/1b carriers were associated with advanced disability (OR: 3.04 (95% CI: 1.22–19.54); p = 0.01), whereas female carriers had an increased likelihood of disease worsening (OR: 1.56 (95% CI: 1.04–2.61); p = 0.03). Our findings suggest that MS may be linked to thrombophilia-related polymorphisms, which warrants further investigation.Keywords
Funding Information
- The Cyprus Institute of Neurology and Genetics (The Cyprus Institute of Neurology and Genetics)
This publication has 59 references indexed in Scilit:
- Plasminogen activator inhibitor-1 4G/5G polymorphism and retinopathy risk in type 2 diabetes: a meta-analysisBMC Medicine, 2013
- Modeling and Molecular Dynamics of HPA-1a and -1b Polymorphisms: Effects on the Structure of the β3 Subunit of the αIIbβ3 IntegrinPLOS ONE, 2012
- Functional Polymorphisms of the Coagulation Factor II Gene (F2) and Susceptibility to Systemic Lupus ErythematosusThe Journal of Rheumatology, 2011
- Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteriaAnnals of Neurology, 2011
- Association of PAI-1 4G/5G and -844G/A Gene Polymorphisms and Changes in PAI-1/Tissue Plasminogen Activator Levels in Myocardial Infarction: A Case–Control StudyGenetic Testing and Molecular Biomarkers, 2010
- Homocysteine–NMDA receptor‐mediated activation of extracellular signal‐regulated kinase leads to neuronal cell deathJournal of Neurochemistry, 2009
- Asociación entre el polimorfismo 4G/5G en el gen del inhibidor del activador del plasminógeno-1 (PAI-1) y el infarto agudo de miocardio con elevación del ST en pacientes jóvenesRevista Espanola de Cardiologia, 2009
- Polymorphisms of the human platelet alloantigens HPA‐1, HPA‐2, HPA‐3, and HPA‐4 in ischemic strokeAmerican Journal of Hematology, 2008
- Plasma homocysteine levels in multiple sclerosisJournal of Neurology, Neurosurgery & Psychiatry, 2006
- The factor V HR2 haplotype: prevalence and association of the A4070G and A6755G polymorphismsBlood Coagulation & Fibrinolysis, 2001