The genetics of carotid dissection: meta-analysis of a MTHFR/C677T common molecular variant.
OBJECTIVE
Carotid dissection is a recognized cause of stroke. An association has been reported between carotid dissection and elevated homocysteine levels. Homocysteine levels are partly determined by a thermolibile form of methyltetrahydrofolate reductase (MTHFR) which has a common C677T single nucleotide polymorphism (SNP). We sought to undertake a comprehensive genetic meta-analysis of this SNP and its association with carotid dissection.


METHODS
All case-control studies evaluating MTHFR/C677T in carotid dissection were identified. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) using both fixed and random effects were determined for both dominant and recessive genetic models. Analyses were also undertaken to compare the effects of the homogenous forms of MTHFR/C677T.


RESULTS
Four manuscripts analyzing a total of 420 individuals (183 cases and 237 controls) were identified. The pooled OR for the dominant MTHFR/T677 model was 1.36 (95% CI 0.89-2.08; p = 0.16) while the pooled OR for the recessive TT model was 1.07 (95% CI 0.61-1.89; p = 0.81). To ensure a subtle recessive effect was not being masked by the inclusion of the heterozygous genotype, comparison of the CC and TT genotypes in cases against controls was undertaken but no significant association was observed (OR 0.73; 95% CI 0.38-1.40; p = 0.34).


CONCLUSIONS
Our data does not support an association between the MTHFR/C677T molecular variant and carotid dissection. As this SNP accounts for the majority of the genetic variance of homocysteine levels, our data suggests that homocysteine is unlikely to play a major role in this condition.
McColgan
Peter
P
Imperial College Cerebrovascular Research Unit (ICCRU), Department of Clinical Neuroscience, Imperial College London & Hammersmith Hospitals, London, UK.
Sharma
Pankaj
P
D020215:Carotid Artery, Internal, Dissection / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D005799:Genes, Dominant; D005808:Genes, Recessive; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide
D006710:Homocysteine; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase