Article
Genetic polymorphisms of homocysteine metabolism are associated with intracranial aneurysms
Assoziation zwischen genetischen Polymorphismen des Homocystein-Stoffwechsels und intrakraniellen Aneurysmata
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Published: | May 30, 2008 |
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Objective: Disturbances of homocysteine metabolism are 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: Two series of Caucasian patients harboring intracranial aneurysms (n=111 and n=144) treated at two hospitals with corresponding controls from the respective geographical areas (n=250 and n=98) were genotyped for the following genetic 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 Ω-1 (GSTO1) c.428C>A, reduced folate carrier 1 (RFC1) c.80G>A, and transcobalamin 2 (Tc2) c.776C>G. Associations were investigated with stratification by center.
Results: The G-allele of Tc2 c.777C>G was found to be under-represented in aneurysma 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=0.0024). We obtained borderline results for the G-allele of RFC1 c.80G>A (OR 1.64; 95% CI 1.01–2.65; p=0.0509) and the insertion-allele of DHFR c.594+59del19bp (OR 1.61; 95% CI 1.00-2.60; p=0.0589), which were found to be over-represented in patients.
Conclusions: Certain polymorphisms of the homocysteine metabolism are associated with the formation of intracranial aneurysms in Caucasians. These data point to a more general role for variations of homocysteine metabolism in aneurysm pathogenesis.