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Association of Variants in FCGR2A, PTPN2, and GM-CSF with Cerebral Cavernous Malformation: Potential Biomarkers for a Symptomatic Disease

[ Vol. 18 , Issue. 2 ]

Author(s):

Gustavo da Fontoura Galváo, Fabrícia Lima Fontes-Dantas, Elielson Veloso da Silva , Soniza Vieira Alves-Leon and Jorge Marcondes de Souza*   Pages 172 - 180 ( 9 )

Abstract:


Background: Cerebral Cavernous Malformations (CCM) predispose patients to a lifetime risk of seizures and symptomatic hemorrhage. Only a small percentage of people affected will develop clinical symptoms and the molecular mechanisms underlying lesional activity remain unclear. We analyzed a panel of Single Nucleotide Polymorphisms (SNPs) in CCM patients. We looked for plasmatic inflammatory cytokines, checking for a pattern of plasma expression heterogeneity and any correlation with genetic variations identified with different CCM clinical phenotypes.

Methods: This was a case-control study from a long-term follow-up cohort including 23 CCM patients, of which 16 were symptomatic, and 7 were asymptomatic. A 200-SNP panel was considered through next-generation sequencing and 18 different plasma molecules were assessed through a suspension array system.

Results: Fcγ receptor IIa rs1801274 (FCGR2A) and protein tyrosine phosphatase non-receptor type 2 rs72872125 PTPN2 were statistically different between groups. Patients who had a combination of the presence of FCGR2A and the absence of PTPN2 also had symptoms earlier in life. The combination of genetic polymorphisms and serum level of GM-CSF showed the best diagnostic biomarker to distinguish symptomatic patients as formulated: [0.296*(FCGR2A)] + [-0.788*(PTPN2)] + [-0.107*(GM-CSF)].

Conclusion: We have shown that SNPs in inflammation genes might be related to a symptomatic phenotype in CCM. We also demonstrated that a formula based on two of these polymorphisms (FCGR2A+ and PTPN2+) is possibly capable of predicting a symptomatic phenotype during a patient’s lifetime.

Keywords:

PTPN2, GM-CSF, cerebral cavernous malformation, biomarkers, Fcγ receptor IIa, peripheral plasma.

Affiliation:

Postgraduate Program in Neurology, Translational Neuroscience Laboratory, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Postgraduate Program in Neurology, Translational Neuroscience Laboratory, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Postgraduate Program in Neurology, Translational Neuroscience Laboratory, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Postgraduate Program in Neurology, Translational Neuroscience Laboratory, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Department of Neurosurgery, Universidade Federal do Rio de Janeiro, Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, RJ



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