title: Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations.
abstract: The B vitamins are components of one-carbon metabolism (OCM) that contribute to DNA synthesis and methylation. Homocysteine, a by-product of OCM, has been associated with coronary heart disease, stroke and neurological disease. To investigate genetic factors that affect circulating vitamin B6, vitamin B12, folate and homocysteine, a genome-wide association analysis was conducted in the InCHIANTI (N = 1175), SardiNIA (N = 1115), and BLSA (N = 640) studies. The top loci were replicated in an independent sample of 687 participants in the Progetto Nutrizione study. Polymorphisms in the ALPL gene (rs4654748, p = 8.30 x 10(-18)) were associated with vitamin B6 and FUT2 (rs602662, [corrected] p = 2.83 x 10(-20)) with vitamin B12 serum levels. The association of MTHFR, a gene consistently associated with homocysteine, was confirmed in this meta-analysis. The ALPL gene likely influences the catabolism of vitamin B6 while FUT2 interferes with absorption of vitamin B12. These findings highlight mechanisms that affect vitamin B6, vitamin B12 and homocysteine serum levels.
authors.affiliation: Medstar Research Institute, Baltimore, MD 21250, USA. tanakato@mail.nih.gov
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka
authors.forename: Paul
authors.initials: P
authors.lastname: Scheet
authors.forename: Betti
authors.initials: B
authors.lastname: Giusti
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Piras
authors.forename: Gianluca
authors.initials: G
authors.lastname: Usala
authors.forename: Sandra
authors.initials: S
authors.lastname: Lai
authors.forename: Antonella
authors.initials: A
authors.lastname: Mulas
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Corsi
authors.forename: Anna
authors.initials: A
authors.lastname: Vestrini
authors.forename: Francesco
authors.initials: F
authors.lastname: Sofi
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Gori
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
authors.forename: Jack
authors.initials: J
authors.lastname: Guralnik
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
authors.forename: Goncalo R
authors.initials: GR
authors.lastname: Abecasis
authors.forename: David
authors.initials: D
authors.lastname: Schlessinger
authors.forename: Manuela
authors.initials: M
authors.lastname: Uda
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005647:Fucosyltransferases / Q000235:genetics; D055106:Genome-Wide Association Study; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics; D014155:Transcobalamins / Q000235:genetics; D014805:Vitamin B 12 / Q000097:blood*; D025101:Vitamin B 6 / Q000097:blood*; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D000469:Alkaline Phosphatase; D005492:Folic Acid; D005647:Fucosyltransferases; D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D014155:Transcobalamins; D014805:Vitamin B 12; D025101:Vitamin B 6; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C521186:NBPF3 protein, human; C029486:intrinsic factor-cobalamin receptor