Furthermore, genome-wide association studies (GWAS) in a large and homogeneous cohort of fCCM cases carrying the same disease-associated KRIT1 mutation showed that polymorphic genes involved in oxidative stress and inflammatory responses, including distinct members of cytochrome P450 (CYP), matrix metalloproteinase (MMP) and Toll-like receptor (TLR) families, act as genetic modifiers of major disease severity phenotypes, such as the development of numerous and large CCM lesions and susceptibility to ICH [20,21,35]. This evidence concerns the gene PPIG and cerebral cavernous malformation.