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Genome-wide Association Study of Vitamin B6, Vitamin B12, Folate, and Homocysteine Blood Concentrations

By Toshiko Tanaka, Paul Scheet, Betti Giusti, Stefania Bandinelli, Maria Grazia Piras, Gianluca Usala, Sandra Lai, Antonella Mulas, Anna Maria Corsi, Anna Vestrini, Francesco Sofi, Anna Maria Gori, Rosanna Abbate, Jack Guralnik, Andrew Singleton, Goncalo R. Abecasis, David Schlessinger, Manuela Uda and Luigi Ferrucci

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 × 10−18) were associated with vitamin B6 and FUT2 (rs6022662, p = 2.83 × 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

Topics: Report
Publisher: Elsevier
OAI identifier: oai:pubmedcentral.nih.gov:2667971
Provided by: PubMed Central
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