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

Abstract

ABSTRACTBiological 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 SNPsVDRrs7975232, VDRrs731236, VDRrs11568820as well as expanded the analysis ofPTPN2rs72872125andFCGR2Ars1801274in 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 thePTPN2rs72872125CT and theVDRrs7975232CC genotype were independently associated with an asymptomatic phenotype. Additionally,PTPN2rs72872125CC genotype and serum level of GM-CSF could predict a diagnostic association with symptomatic phenotype in CCM patients, while theFCGR2Ars1801274GG genotype could predict a symptomatic event during follow-up. The study also found a correlation betweenVDRrs731236AA andVDRrs11568820CC 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.