Plasma homocysteine concentration, C677T MTHFR genotype, and 844ins68bp CBS genotype in young adults with spontaneous cervical artery dissection and atherothrombotic stroke.
OBJECTIVE
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 micromol/L; range, 7 to 32.8 micromol/L) compared with control subjects (8.9 micromol/L; range, 5 to 17.3 micromol/L; 95% CI, 1.05 to 1.52; P=0.006). Cases with tHcy concentration above the cutoff level of 12 micromol/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.
Pezzini
Alessandro
A
Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia. ale_pezzini@hotmail.com
Del Zotto
Elisabetta
E
Archetti
Silvana
S
Negrini
Riccardo
R
Bani
Paolo
P
Albertini
Alberto
A
Grassi
Mario
M
Assanelli
Deodato
D
Gasparotti
Roberto
R
Vignolo
Luigi Amedeo
LA
Magoni
Mauro
M
Padovani
Alessandro
A
D000328:Adult; D019943:Amino Acid Substitution; D002545:Brain Ischemia / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D020215:Carotid Artery, Internal, Dissection / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D015897:Comorbidity; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D007558:Italy / Q000453:epidemiology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D011446:Prospective Studies; D012016:Reference Values; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D020217:Vertebral Artery Dissection / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism
D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)