TY - JOUR
T1 - Genome-wide Association Study of Vitamin B6, Vitamin B12, Folate, and Homocysteine Blood Concentrations
AU - Tanaka, Toshiko
AU - Scheet, Paul
AU - Giusti, Betti
AU - Bandinelli, Stefania
AU - Piras, Maria Grazia
AU - Usala, Gianluca
AU - Lai, Sandra
AU - Mulas, Antonella
AU - Corsi, Anna Maria
AU - Vestrini, Anna
AU - Sofi, Francesco
AU - Gori, Anna Maria
AU - Abbate, Rosanna
AU - Guralnik, Jack
AU - Singleton, Andrew
AU - Abecasis, Goncalo R.
AU - Schlessinger, David
AU - Uda, Manuela
AU - Ferrucci, Luigi
N1 - Funding Information:
The InCHIANTI study baseline (1998-2000) was supported as a “targeted project” (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the U.S. National Institute on Aging (Contracts: 263 MD 9164 and 263 MD 821336); the InCHIANTI Follow-up 1 (2001–2003) was funded by the U.S. National Institute on Aging (Contracts: N.1-AG-1-1 and N.1-AG-1-2111); the InCHIANTI Follow-ups 2 and 3 studies (2004-2010) were financed by the U.S. National Institute on Aging (Contract: N01-AG-5-0002). BLSA and InCHIANTI were supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health (NIH), Baltimore, Maryland. A portion of that support was through a R&D contract with MedStar Research Institute. The SardiNIA team was supported by Contract NO1-AG-1-2109 from the NIA. The replication experiments were supported by a grant from Genopolis government FIRB project (RBLA038RMA_008).
PY - 2009/4/10
Y1 - 2009/4/10
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajhg.2009.02.011
DO - 10.1016/j.ajhg.2009.02.011
M3 - Article
C2 - 19303062
AN - SCOPUS:64149102559
SN - 0002-9297
VL - 84
SP - 477
EP - 482
JO - American journal of human genetics
JF - American journal of human genetics
IS - 4
ER -