Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations

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, vitam...

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Published in:American journal of human genetics Vol. 84; no. 4; p. 477
Main Authors: Tanaka, Toshiko, Scheet, Paul, Giusti, Betti, Bandinelli, Stefania, Piras, Maria Grazia, Usala, Gianluca, Lai, Sandra, Mulas, Antonella, Corsi, Anna Maria, Vestrini, Anna, Sofi, Francesco, Gori, Anna Maria, Abbate, Rosanna, Guralnik, Jack, Singleton, Andrew, Abecasis, Goncalo R, Schlessinger, David, Uda, Manuela, Ferrucci, Luigi
Format: Journal Article
Language:English
Published: United States 01.04.2009
Subjects:
Adult
Aged
Aged, 80 and over
Alkaline Phosphatase - genetics
Female
Folic Acid - blood
Fucosyltransferases - genetics
Galactoside 2-alpha-L-fucosyltransferase
Genome-Wide Association Study
Homocysteine - blood
Humans
Male
Methylenetetrahydrofolate Reductase (NADPH2) - genetics
Middle Aged
Neoplasm Proteins - genetics
Polymorphism, Single Nucleotide
Receptors, Cell Surface - genetics
Transcobalamins - genetics
Vitamin B 12 - blood
Vitamin B 6 - blood
ISSN:1537-6605, 1537-6605
Online Access:Get more information
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Summary: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.
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ISSN:1537-6605
1537-6605
DOI:10.1016/j.ajhg.2009.02.011