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lüll The genetics of cervical artery dissection: a systematic review Debette S; Markus HSStroke 2009[Jun]; 40 (6): e459-66BACKGROUND AND PURPOSE: The pathophysiology of cervical artery dissections (CAD), a major cause of ischemic stroke in young adults, is poorly understood. Several arguments suggest a genetic predisposition. METHODS: We systematically reviewed all published data on genetic risk factors for CAD and performed a meta-analysis of association studies with the MTHFR C677T polymorphism. RESULTS: Rarely, CAD is associated with a known monogenic connective tissue disease, mainly vascular Ehlers-Danlos syndrome. However, in the large majority of CAD cases, there is no evidence for a known monogenic disease. Several arguments, including the association of CAD with dermal connective tissue abnormalities that are inherited, suggest that genetic factors also play a role in "sporadic" CAD as part of a multifactorial predisposition. We identified 15 genetic association studies: 10 were negative and 5 reported associations of 3 genetic variants in 3 different candidate genes. Two studies reported associations with polymorphisms in ICAM-1 and COL3A1, but neither has been replicated. Three studies reported an association with the MTHFR 677TT genotype, but 3 other studies did not replicate this. A meta-analysis of these data identified an overall significant association of the MTHFR 677TT genotype with CAD (OR, 1.67; 95% CI, 1.21 to 2.31). We also identified 9 studies screening candidate genes for mutations and 4 linkage studies, yielding mostly negative results. CONCLUSIONS: Although several interesting hypotheses were generated, the majority of genetic studies in CAD have been negative until now, but they were markedly underpowered. Progress in unraveling the genetics of CAD will require the collection of DNA samples from large multicenter series.|Adult[MESH]|Cerebral Arterial Diseases/complications/epidemiology/*genetics[MESH]|Gene Frequency[MESH]|Genetic Linkage[MESH]|Humans[MESH]|Stroke/epidemiology/etiology/*genetics[MESH]|Young Adult[MESH] |