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Annals of neurology · Apr 2010
Multicenter StudyMatrix metalloproteinase-3 and intracranial arterial dolichoectasia.
- Fernando Pico, Marie-Paule Jacob, Julien Labreuche, Nadem Soufir, Pierre-Jean Touboul, Joëlle Benessiano, François Cambien, Bernard Grandchamp, Jean-Baptiste Michel, and Pierre Amarenco.
- Neurology Department, Versailles Hospital and Versailles Saint-Quentin-en-Yvelines University, Versailles, France.
- Ann. Neurol. 2010 Apr 1;67(4):508-15.
ObjectiveIntracranial arterial dolichoectasia (IADE), also called dilatative arteriopathy of the brain, is defined as an increase in length and diameter of intracranial arteries. Abdominal aortic aneurysm and ectasia of coronary arteries have been reported in association with IADE. In both conditions, a dysfunction of matrix metalloproteinases (MMP)-2, -3, and -9 have been found. Our aim was to investigate these MMP pathways in stroke patients with IADE.MethodsFive hundred ten Caucasians patients with brain infarction were consecutively recruited at 12 centers. The diagnosis of IADE was made by consensus between 2 neurologists based on magnetic resonance imaging scans. Determination of MMP-2, -3, and -9 plasma levels was centralized in 1 laboratory. Because we found a threshold effect of MMP-3 plasma levels with the risk of IADE, determination of the MMP-3 5A/6A polymorphism was carried out.ResultsIADE was identified in 12% of stroke patients. There was no association of IADE with mean MMP-2, -3, and -9 plasma levels. After categorization of MMP plasma levels into tertiles, we found a higher risk of IADE with the lowest MMP-3 tertile (adjusted odds ratio [OR], 2.48; 95% confidence interval [CI], 1.17-5.23). In genotype analysis, there was a significant additive effect of the 5A allele on the risk of IADE, with an adjusted OR of 1.62 (95% CI, 1.03-2.55).InterpretationIn this cohort of stroke patients of Caucasian ancestry, IADE was associated with low MMP-3 plasma levels and with the 5A/6A polymorphism of the promoter region of MMP-3. These results suggest that MMP-3 may play a role in IADE.
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