Contribution of the 9p21.3 genomic region to the pathogenesis of cerbrovascular disorders in the Italian population.

Stroke is the third most common cause of death and the major cause of adult neurological disability, representing an important health issue. Cerebrovascular disorders, particularly ischemic stroke, are complex diseases in which several genetic variants interact with environmental factors to determine phenotypic manifestations. The identification of such genetic factors is essential to improve risk prediction and to gain insight into pathophysiological mechanisms and it will eventually allow the development of new therapeutic strategies. We are studying an Italian cohort of patients affected by cerebrovascular disorders: a total of 712 cases have been recruited and genotyped on the Illumina platform for more than 600k whole-genome SNPs, together with a total of 961 healthy individuals selected as controls (in part recruited in collaboration with the PROCARDIS consortium). A case-control genome-wide association study is now ongoing in order to validate previously recognized risk variant and to identify new genetic determinants. In particular we are studying the association of genetic variants at 9p21.3, a genomic region already known to be involved in the pathogenesis of different disorders, in the Italian Cerebrovascular Cohort. Results of our analysis demonstrated that genetic variants in this region represent risk factors for Cerebrovascular disorders also in the Italian population and highlighted the preferential association to the subgroup of patients affected by vascular dementia.