Is There Evidence of Genetic Variation in Folate and Homocysteine Levels?
The original proposal that hyperhomocysteinemia might be important in atherosclerosis came from work by McCully14 on the vascular pathology of the inborn error of metabolism, homocystinuria. However, carriers for homocystinuria (1 in 400 population), who have half-deficiency of cystathionine ß-synthase, rarely account for the homocysteine elevations observed in vascular disease.15 A common thermolabile variant of the enzyme MTHFR is homozygous in 10% to 13% of the Caucasian population (TT genotype). Such individuals, particularly in the presence of suboptimal folate nutrition, tend to have slightly elevated homocysteine levels.16 In two different European studies, 35% of working men in the top decile of tHcy levels had the TT genotype,17 as did almost everyone with tHcy levels of >20 µmol/L.18 Despite several reports that the TT genotype is increased among patients with premature vascular disease,16 no such association could be demonstrated in 2029 patients with coronary heart disease
