Assessment of tailor-made prevention of atherosclerosis with folic acid supplementation: randomized, double-blind, placebo-controlled trials in each MTHFR C677T genotype.
This study aimed at assessing the effect of folic acid supplementation quantitatively in each MTHFR C677T genotype and considered the efficiency of tailor-made prevention of atherosclerosis. Study design was genotype-stratified, randomized, double-blind, placebo-controlled trials. The setting was a Japanese company in the chemical industry. Subjects were 203 healthy men after exclusion of those who took folic acid or drugs known to effect folic acid metabolism. Intervention was folic acid 1 mg/day p.o. for 3 months. The primary endpoint was plasma total homocysteine level (tHcy). In all three genotypes, there were significant tHcy decreases. The greatest decrease was in the TT homozygote [6.61 (3.47-9.76) micromol/l] compared with other genotypes [CC: 2.59 (1.81-3.36), CT: 2.64 (2.16-3.13)], and there was a significant trend between the mutated allele number and the decrease. The tHcy were significantly lowered in all the genotypes, but the amount of the decrease differed significantly in each genotype, which was observed at both 1 and 3 months. Using these time-series data, the largest benefit obtained by the TT homozygote was appraised as 2.4 times compared with the CC homozygote. Taking into account the high allele frequency of this SNP, this quantitative assessment should be useful when considering tailor-made prevention of atherosclerosis with folic acid.
Miyaki
Koichi
K
Department of Preventive Medicine and Public Health, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. miyaki@sc.itc.keio.ac.jp.
Murata
Mitsuru
M
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.|Department of Laboratory Medicine, School of Medicine, Keio University, Tokyo, Japan.
Kikuchi
Haruhito
H
Department of Laboratory Medicine, School of Medicine, Keio University, Tokyo, Japan.
Takei
Izumi
I
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.|Department of Laboratory Medicine, School of Medicine, Keio University, Tokyo, Japan.
Nakayama
Takeo
T
Department of Health Informatics, Kyoto University School of Public Health, Kyoto, Japan.
Watanabe
Kiyoaki
K
Department of Laboratory Medicine, School of Medicine, Keio University, Tokyo, Japan.
Omae
Kazuyuki
K
Department of Preventive Medicine and Public Health, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
D000483:Alleles; D001161:Arteriosclerosis / Q000201:enzymology / Q000235:genetics* / Q000517:prevention & control*; D019587:Dietary Supplements; D004311:Double-Blind Method; D005492:Folic Acid / Q000097:blood; D005494:Folic Acid Deficiency; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006720:Homozygote; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*
D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)