Genetic approaches in the study of risk factors for cervical artery dissection

Front Neurol Neurosci. 2005:20:30-43. doi: 10.1159/000088133.

Abstract

The familial risk of spontaneous cervical artery dissections (sCAD) and the prevalence of the disease in the general population are not well known, making it difficult to estimate the importance of genetic risk factors in sCAD. sCAD is associated in rare cases with inherited diseases such as Ehlers-Danlos syndrome or osteogenesis imperfecta. In most instances, however, sCAD occurs in the absence of known heritable diseases. Genetic risk factors might play a role in further associated conditions, like the ultrastructural connective tissue alterations that are found in skin biopsies of most patients. Systematic mutation search in genes known for their implication in connective tissue disorders has been disappointing apart from rare missense mutations in the genes encoding type V collagen that were found in a minority of patients with sCAD. Efforts are now focusing on genetic linkage studies scanning the whole genome for markers that cosegregate with the above-mentioned dermal connective tissue alterations. Concomitantly, genetic association studies tested the association between sCAD and candidate genes that were selected a priori on pathophysiological arguments, in particular genes playing a role in the extracellular matrix, endothelial function, or inflammatory processes. Most association studies reported until now were negative, apart from one showing an association with a polymorphism in the MTHFR gene and another with a polymorphism in the ICAM-1 gene. However, the results of the association studies published so far must be interpreted cautiously because of the small sample sizes.

Publication types

  • Review

MeSH terms

  • Arteries / metabolism
  • Arteries / pathology
  • Arteries / physiopathology
  • Carotid Artery, Internal, Dissection / genetics*
  • Carotid Artery, Internal, Dissection / physiopathology
  • Chromosome Mapping / methods
  • Chromosome Mapping / trends
  • Connective Tissue Diseases / complications*
  • Connective Tissue Diseases / diagnosis
  • Connective Tissue Diseases / genetics*
  • DNA Mutational Analysis / methods
  • DNA Mutational Analysis / trends
  • Female
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing / methods
  • Genetic Testing / trends
  • Humans
  • Male
  • Risk Factors
  • Vertebral Artery Dissection / genetics*
  • Vertebral Artery Dissection / physiopathology

Substances

  • Genetic Markers