Role of a common mutation in the homocysteine regulatory enzyme methylenetetrahydrofolate reductase in ischemic stroke

A common mutation in methylenetetrahydrofolate reductase (MTHFR), a homocys teine metabolic pathway enzyme, has been associated with increased homocyst eine levels and increased risk for premature cardiovascular disease. The pu rpose of this study was to assess the association between the prevalence of the MTHFR mutation, hyperhomocysteinemia, and subtypes of ischemic strobe in an elderly population comprised of three age-balanced groups of patients . The presence of the C677T MTHFR mutation was determined by a direct polym erase chain reaction-based assay performed on blood samples from 136 patien ts with acute ischemic stroke, 95 patients with atherosclerotic risk factor s for stroke (including some with a history of previous stroke or transient ischemic attack), and 52 healthy control subjects. The prevalence of the h omozygous C677T mutation was not significantly higher in the elderly stroke patients (7%) than in the atherosclerotic risk (8%) or healthy elderly con trol(246) groups. Plasma homocysteine levels were higher in the acute strok e patient group (14.5 +/- 4.5 mu mol/L) and atherosclerotic risk patient gr oup (14.6 +/- 6.2 mu mol/L) compared with the control subjects (10.3 +/- 3. 1 mu mol/L, P < 0.03). Homozygotes for the C677T MTHFR mutation did not hav e significantly higher homocysteine levels than non-homozygotes. Moderate h yperhomocysteinemia, though common in older patients with ischemic cerebrov ascular disease, is not attributable, at least in this patient group, to a higher prevalence of the C677T MTHFR mutation.