Association of cerebrovascular disease with inflammatory polymorphisms with special reference to cerebral microangiopathy

Cerebral microangiopathy represents a major differential diagnosis in the pathogenesis of dementia. We present preliminary data indicating that (apart from conventional risk factors) genetic constitution determines the risk of cerebrovascular disease. Inflammation is increasingly implicated as primary trigger of atherosclerosis and consecutive angiopathy. However data for the subgroup of microangiopathy are inconsistent. We hypothesize that microangiopathic patients are characterized by a proinflammatory condition mediated by a certain constellation of polymorphisms in genes encoding for inflammatory cytokines. We investigated functional polymorphisms of IL-1β, IL1-receptor, tnf-αIL-6 and MCP-1 genes as well as a polymorphism in the gene encoding for the p22^phox NAD(P)H-oxidase subunit, which proved to be associated with enhanced production of reactive oxygen species (macroangiopathy: n=100; microangiopathy n=28; controls n=100). Macroangiopathy was demonstrated to be significantly associated with a „proinflammatory genetic constitution“. Data for microangiopathy reveal a similar trend, which warrants further investigation in a larger patient collective.