Genetic Markers and Predictive Factors Influencing the Aggressive Behavior of Cerebral Cavernous Malformation

ABSTRACT Biological behavior of Cerebral Cavernous Malformation (CCM) is still controversial without clear-cut signature for biological mechanistic explanation of lesion aggressiveness. There is plenty evidence implicating dysregulated inflammatory and immune responses in vascular malformation pathogenesis, including CCM. In the present study, we evaluated the predictive capacity of the SNPs VDR rs7975232 , VDR rs731236 , VDR rs11568820 as well as expanded the analysis of PTPN2 rs72872125 and FCGR2A rs1801274 in relation to the aggressive behavior of CCM and its implications in biological processes. This was a single-site prospective observational cohort study with 103 patients enrolled, 42 had close follow-up visits for a period of 4 years, focused on 2 main aspects of the disease: (1) symptomatic event that composed both intracranial bleeding or epilepsy and (2) precocity of symptoms. We report a novel observation that the PTPN2 rs72872125 CT and the VDR rs7975232 CC genotype were independently associated with an asymptomatic phenotype. Additionally, PTPN2 rs72872125 CC genotype and serum level of GM-CSF could predict a diagnostic association with symptomatic phenotype in CCM patients, while the FCGR2A rs1801274 GG genotype could predict a symptomatic event during follow-up. The study also found a correlation between VDR rs731236 AA and VDR rs11568820 CC genotype to the time to first symptomatic event. In summary, this study provides valuable insights into the genetic markers that could potentially impact the development and advancement of CCM.