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Genetics of Cervical Artery Dissection

  • Stéphanie Debette
Chapter

Abstract

Despite being relatively rare in the general population, cervical artery dissection (CEAD) is a major cause of ischemic stroke in young and middle-aged adults. Its risk factors and underlying mechanisms are poorly understood. Seldom, CEAD can be caused by a monogenic connective tissue disease, mainly vascular Ehlers-Danlos syndrome. In the absence of a known monogenic connective tissue disorder, a small proportion of CEAD patients (<3%) have a family history of symptomatic CEAD, and in some series, about half of CEAD patients were shown to have skin connective tissue abnormalities segregating in families according to an autosomal dominant pattern. A few linkage studies were performed that have so far yielded negative results. In the majority of CEAD cases, a number of arguments suggest that genetic factors might play a role as part of a multifactorial predisposition. Seventeen genetic association studies have been published, which tested the association of various candidate genes with CEAD. Most of these studies were negative. Two studies reported associations with polymorphisms in the ICAM1 and COL3A1 genes, but neither has been replicated. Three studies reported an association with the MTHFR 677TT genotype, but four others did not replicate this. A meta-analysis suggested an overall weak association of the MTHFR 677TT genotype with CEAD. Genetic association studies so far have been limited by small sample size, due to the low incidence of the disease, and by the use of a candidate gene approach, with limited exploration of genetic variation in a small number of genes that were chosen based on a priori hypotheses. International efforts have recently been made to gather much larger samples through multicenter recruitment, and a genome-wide association study is currently under way, which aims at identifying novel genetic variants associated with CEAD, using an unbiased approach.

Keywords

Aortic Dissection Autosomal Dominant Polycystic Kidney Disease Genetic Association Study Marfan Syndrome COL3A1 Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Springer-Verlag London 2013

Authors and Affiliations

  1. 1.Department of NeuroepidemiologyInserm U708, Salpêtrière HospitalParis Cedex 13France
  2. 2.Department of EpidemiologyUniversity of Versailles Saint-Quentin en Yvelines, Raymond Poincarè HospitalGarchesFrance

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