Polymorphisms of homocysteine metabolism are associated with intracranial aneurysms.
BACKGROUND
Impaired homocysteine metabolism is associated with a number of vasculopathies including extracranial aneurysms. We analyzed the possible association of nine genetic variants of homocysteine metabolism with the occurrence of intracranial aneurysms.


METHODS
Caucasian patients (n = 255) treated at two German hospitals for intracranial aneurysms and local controls (n = 348) were genotyped for the following polymorphisms: methionine synthase (MTR) c.2756A-->G, methylenetetrahydrofolate reductase (MTHFR) c.677C-->T, MTHFR c.1298A-->C, cystathionine beta-synthase (CBS) c.844_855ins68, CBS c.833T-->C, dihydrofolate reductase (DHFR) c.594 + 59del19bp, glutathione S-transferase Omega-1 (GSTO1) c.428C-->A, reduced folate carrier 1 (RFC1) c.80G-->A and transcobalamin 2 (Tc2) c.776C-->G.


RESULTS
The G-allele of the missense polymorphism Tc2 c.777C-->G was found to be underrepresented in patients, suggesting that this variant may protect from the formation of cerebral aneurysms [odds ratio per two risk alleles (OR) 0.48; 95% confidence interval (CI) 0.30-0.77; p = 0.002]. We obtained borderline results for the G-allele of RFC1 c.80G-->A (OR 1.64; 95% CI 1.01-2.65; p = 0.051) and the insertion allele of DHFR c.594 + 59del19bp (OR 1.61; 95% CI 1.00-2.60; p = 0.059), which were found to be overrepresented in patients.


CONCLUSIONS
Polymorphisms of homocysteine metabolism are possible risk factors for the formation of intracranial aneurysms.
Semmler
Alexander
A
Department of Neurology, University of Bonn, Bonn, Germany.
Linnebank
Michael
M
Krex
Dietmar
D
Götz
Anika
A
Moskau
Susanna
S
Ziegler
Andreas
A
Simon
Matthias
M
D000328:Adult; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000235:genetics / Q000378:metabolism; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics / Q000378:metabolism; D058973:Folate Receptors, GPI-Anchored; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D002532:Intracranial Aneurysm / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D014155:Transcobalamins / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D014155:Transcobalamins; D006710:Homocysteine; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013762:Tetrahydrofolate Dehydrogenase; D005982:Glutathione Transferase; D003541:Cystathionine beta-Synthase