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

Elevated plasma homocyst(e)ine [H(e)] concentration is associated with premature atherosclerosis. A common cause of elevated plasma H(e) concentration is a thermolabile mutation (677T) in the gene encoding methylenetetrahydrofolate reductase (MTHFR). We sought to determine whether plasma H(e) concentration or MTHFR genotype would be more strongly associated with carotid plaque area (CPA), a potential intermediate phenotype of atherosclerosis. In 307 subjects who were ascertained through a premature atherosclerosis clinic, we measured CPA with 2-dimensional ultrasound and also determined traditional atherosclerosis risk factors, in addition to plasma H(e) concentration and MTHFR genotypes. We found that the frequency of the MTHFR 677T allele was 0.363 in this 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 micromol/L, respectively, P