Plasma homocyst(e)ine concentration, but not MTHFR genotype, is associatedwith variation in carotid plaque area

Background and Purpose-Elevated plasma homocyst(e)ine [H(e)] concentration is associated with premature atherosclerosis, A common cause of elevated pl asma H(e) concentration is a thermolabile mutation (677T) in the gene encod ing methylenetetrahydrofolate reductase (MTHFR). We sought to determine whe ther plasma H(e) concentration or MTHFR genotype would be more strongly ass ociated with carotid plaque area (CPA), a potential intermediate phenotype of atherosclerosis, Methods-In 307 subjects who were ascertained through a premature atheroscle rosis clinic, we measured CPA with 2-dimensional ultrasound and also determ ined traditional atherosclerosis risk factors, in addition to plasma H(e) c oncentration and MTHFR genotypes, Results-We found that the frequency of the MTHFR 677T allele was 0.363 in t his sample. Mean plasma H(e) concentration was significantly higher in 677T /T homozygotes than in 677T/C heterozygotes and 677C/C homozygotes (17.1+/- 13.7 versus 13.5+/-6.1 versus 12.6+/-5.9 mu mol/L, respectively, P<0.001), Analysis of variance showed that CPA was significantly associated with age, sex, smoking, diabetes, hypertension, and hyperlipidemia (each P<0.05). Wh en plasma H(e) concentration was included in the model, it was significantl y associated with CPA (P<0.05), However, when the MTHFR genotype was includ ed in the model, it was not associated with CPA (P=0.50), Furthermore, ther e was a significant correlation of CPA with plasma H(e) (r=0.23, P<0.0001). However, the moan CPA did not differ between subjects according to genotyp e. Conclusions-Thus, plasma H(e), but not MTHFR genotype, is significantly ass ociated with carotid atherosclerosis, suggesting that the biochemical test may be sufficient to identify patients who may be at increased risk of athe rosclerosis through this mechanism.