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Stroke. 2002;33:664-669
doi: 10.1161/hs0302.103625
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(Stroke. 2002;33:664.)
© 2002 American Heart Association, Inc.


Original Contributions

Plasma Homocysteine Concentration, C677T MTHFR Genotype, and 844ins68bp CBS Genotype in Young Adults With Spontaneous Cervical Artery Dissection and Atherothrombotic Stroke

Alessandro Pezzini, MD; Elisabetta Del Zotto, MD; Silvana Archetti, PhD; Riccardo Negrini, MD; Paolo Bani, MD; Alberto Albertini, MD; Mario Grassi, PhD; Deodato Assanelli, MD; Roberto Gasparotti, MD; Luigi Amedeo Vignolo, MD; Mauro Magoni, MD Alessandro Padovani, MD, PhD

From Clinica Neurologica (A.P., E. Del Z., L.A.V., M.M., A.P.); III Laboratorio di Analisi, Biotecnologie (S.A., R.N., P.B., A.A.); Clinica Cardiologica (D.A.); and Dipartimento di Radiologia, Neuroradiologia (R.G.), Università degli Studi di Brescia, Brescia, Italia, and Istituto di Statistica Medica e Biometria, Università degli Studi di Pavia (M.G.), Pavia, Italia.

Correspondence to Alessandro Pezzini, Clinica Neurologica, Università degli Studi di Brescia, P. le Spedali Civili, 1, 25100, Brescia, Italia. E-mail ale_pezzini{at}hotmail.com

Background and Purpose The role of mild hyperhomocysteinemia as a risk factor for cerebral ischemia may depend on stroke subtype. To test this hypothesis, we undertook a prospective case-control study of a group of patients with spontaneous cervical artery dissection (sCAD), a group of patients with atherothrombotic stroke (non-CAD), and a group of control subjects.

Methods Fasting total plasma homocysteine (tHcy) concentration, C677T MTHFR genotype, and 844ins68bp CBS genotype were determined in 25 patients with sCAD, 31 patients <45 years of age with non-CAD ischemic stroke, and 36 control subjects. Biochemical data in the patient groups were obtained within the first 72 hours of stroke onset.

Results Median tHcy levels were significantly higher in patients with sCAD (13.2 µmol/L; range, 7 to 32.8 µmol/L) compared with control subjects (8.9 µmol/L; range, 5 to 17.3 µmol/L; 95% CI, 1.05 to 1.52; P=0.006). Cases with tHcy concentration above the cutoff level of 12 µmol/L were significantly more represented in the group of patients with sCAD compared with control subjects (64% versus 13.9%; 95% CI, 2.25 to 44.23; P=0.003); a significant association between the MTHFR TT genotype and sCAD was also observed (36% versus 11.1%; 95% CI, 1.10 to 19.23; P=0.045). No significant difference in tHcy levels and in the prevalence of thermolabile MTHFR was found between patients with non-CAD ischemic stroke and control subjects and between patients with sCAD and non-CAD ischemic stroke. The distribution of the 844ins68bp CBS genotype and the prevalence of subjects carrying both the TT MTHFR and 844ins68bp CBS genotypes were not significantly different among the 3 groups.

Conclusions Our results are consistent with the hypothesis that increased plasma homocysteine levels and the TT MTHFR genotype may represent risk factors for sCAD. In contrast, their role in atherothrombotic strokes remains a contentious issue.


Key Words: cervical artery dissection • cystathionine ß-synthase • homocysteine • methylenetetrahydrofolate reductase




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