Genes for stroke

Identifying the genes involved in multifactorial stroke Half the risk of ischaemic stroke remains unexplained by conventional risk factors1 and genetic predisposition has been widely speculated to account for some of this unexplained risk.2 Although significant progress has been made unravelling the basis of single gene stroke disorders, identifying the underlying genes for common or multifactorial stroke, for which there is no obvious Mendelian pattern of inheritance, has proved difficult. Has this situation changed with the recent publication of the first independent risk gene for common stroke?3 What is the evidence that genetic risk factors are important in stroke risk? Twin studies suggest a modest genetic component, more important in younger individuals.4,5 Many studies have determined whether a family history of stroke is more common in stroke cases compared with normal controls.2,6 Most report an association, which is stronger both in younger individuals and with certain stroke subtypes, particularly small vessel disease (lacunar) and large vessel atherosclerotic stroke.7,8 Animal studies have implicated the existence of independent stroke genes. The spontaneously hypertensive stroke prone rat suffers both early onset stroke and larger infarcts in response to experimental middle cerebral artery occlusion. Chromosomal loci have been identified for both of these traits, although the responsible genes remain elusive.9,10 By crossing this animal with the spontaneously hypertensive rat, it has been demonstrated that these influences act independently of hypertension. A large number of single gene disorders can cause stroke (table 1) but most of these are extremely rare.2 It is now apparent that CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) is the most common single gene disorder leading to ischaemic stroke, and is much more frequent than was previously appreciated. True estimates of prevalence are difficult because of …