The influence of genetics on intracranial aneurysm formation and rupture: current knowledge and its possible impact on future treatment

Abstract

The etiology of intracranial aneurysm formation and rupture remains mostly unknown, but lately several studies have increasingly supported the role of genetic factors. In reports so far, genome-wide linkage studies suggest several susceptibility loci that may contain one or more predisposing genes. Depending on the examined ethnic population, several different non-matching chromosomal regions have been found. Studies of several candidate genes report association with intracranial aneurysms. To date, no single gene has been identified as responsible for intracranial aneurysm formation or rupture. In addition to the well-published environmental factors, such as alcohol intake, hypertension and smoking, only the recent progress in molecular genetics enables us to investigate the possible genetic determinants of this disease. Although a familial predisposition is the strongest risk factor for the development of intracranial aneurysms, the mode of Mendelian inheritance is uncertain in most families. Therefore, multiple genetic susceptibilities in conjunction with the environmental factors are considered to act together in the disease's etiology. Accordingly, researchers performed linkage studies and case-control association studies for the genetic analysis and have identified several genes to be susceptible to intracranial aneurysms. The identification of susceptible genes may lead to the understanding of the mechanism of formation and rupture and possibly lead to the development of a pharmacological therapy. Furthermore, should it be possible to identify a genetic marker associated with an increased risk of formation and rupture of an intracranial aneurysm, the necessity for screening and urgency of treatment could be determined more easily. In this review we summarize the current knowledge of intracranial aneurysm genetics and also discuss the method to detect the causalities. In view of the recent advances made in this field, we also give an outlook on possible future genetically engineered therapies, whose development are well underway.