Title:Association of Variants in FCGR2A, PTPN2, and GM-CSF with Cerebral Cavernous Malformation: Potential Biomarkers for a Symptomatic Disease
Volume: 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*
Affiliation:
- Department of Neurosurgery, Universidade Federal do Rio de Janeiro, Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, RJ,Brazil
Keywords:
PTPN2, GM-CSF, cerebral cavernous malformation, biomarkers, Fcγ receptor IIa, peripheral plasma.
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.
