title: Low folate levels may be an atherogenic factor regardless of homocysteine levels in young healthy nonsmokers.
abstract: Low folate and high homocysteine levels are emerging as important risk factors for atherosclerosis and predictors of early coronary heart disease. We evaluated folate and homocysteine levels, compared them with endothelial function, and analyzed their association with the methylenetetrahydrofolate reductase (MTHFR) and endothelial nitric oxide synthase genotypes. We recruited 71 young healthy male nonsmokers without overt cardiovascular or renal disease. Plasma homocysteine levels were enhanced 2-fold in the subjects with the MTHFR 677T/T compared with the others (P = .0001) and also enhanced in the subjects with the endothelial nitric oxide synthase -786C allele (P = .031). Homocysteine levels were independently predicted only by the MTHFR genotype. A relationship between folate and homocysteine levels was not significant. Plasma folate levels were associated independently either with high-density lipoprotein cholesterol levels or with endothelial function in the brachial artery. These results suggest that low folate levels may be a risk factor for cardiovascular diseases regardless of homocysteine levels and that the subjects with lower folate levels should be recommended for dietary folic acid supplementation to elevate endothelial function and probably increase high-density lipoprotein cholesterol levels.
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Imamura
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Murakami
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Takahashi
authors.forename: Xian Wu
authors.initials: XW
authors.lastname: Cheng
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Numaguchi
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.forename: Kenji
authors.initials: K
authors.lastname: Okumura
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000201:enzymology / Q000378:metabolism*; D005492:Folic Acid / Q000097:blood / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D018709:Statistics, Nonparametric; D014280:Triglycerides / Q000097:blood; D018608:Ultrasonography, Doppler
chemical_list: D001786:Blood Glucose; D002784:Cholesterol; D004247:DNA; D005492:Folic Acid; D006442:Glycated Hemoglobin; D006710:Homocysteine; D007328:Insulin; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D052250:Nitric Oxide Synthase Type III; D014280:Triglycerides; C496314:NOS3 protein, human