Homozygous thermolabile variant of the methylenetetrahydrofolate reductasegene: a potential risk factor for hyperhomocysteinaemia, CVD, and stroke in childhood

In this study of 118 children (median age 5.1 years; range 6 months to 17 y ears) with ischaemic stroke or transient ischaemic attack (TIA), 22 childre n (19%) were homozygous for the thermolabile variant of the methylenetetrah ydrofolate reductase allele (t-MTHFR), compared with nine of 78 (12%) of a reference population (p=0.18, OR 1.76, 95% CI 0.76 to 4.04). Of those with cerebrovascular disease (CVD), 17 of 84 mere homozygous for the t-MTHFR all ele (p=0.13 compared with the reference population (OR 1.95, 95% CI 0.81 to 4.65). There was a significant (p<0.025) increment of plasma total homocys teine concentration in homozygotes for the t-MTHFR allele compared with het erozygotes, negatives for the t-MTHFR allele, and control children with no history of stroke. In four of 12 homozygotes for the t-MTHFR allele, plasma homocysteine levels were raised, compared with three of 38 of those who me re negative or heterozygous (p=0.047; OR 5.8, 95% CI 1.1 to 31.2). Homozygo tes for the t-MTHFR allele were significantly more likely to have a recurre nt event than those who were negative or heterozygous (Cox regression p=0.0 31, hazard ratio 2.18, 95% CI 1.08 to 4.42). These data suggest that homozy gosity for the t-MTHFR allele is associated with raised homocysteine levels in children and is a risk factor for primary and secondary stroke and TIA.