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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Vydané v:	American journal of human genetics Ročník 84; číslo 4; s. 477
Hlavní autori:	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
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 01.04.2009
Predmet:	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
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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.
AbstractList	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.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. 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.
Author	Uda, Manuela Tanaka, Toshiko Gori, Anna Maria Bandinelli, Stefania Piras, Maria Grazia Singleton, Andrew Lai, Sandra Guralnik, Jack Schlessinger, David Giusti, Betti Usala, Gianluca Abbate, Rosanna Abecasis, Goncalo R Vestrini, Anna Mulas, Antonella Sofi, Francesco Corsi, Anna Maria Ferrucci, Luigi Scheet, Paul
Author_xml	– sequence: 1 givenname: Toshiko surname: Tanaka fullname: Tanaka, Toshiko email: tanakato@mail.nih.gov organization: Medstar Research Institute, Baltimore, MD 21250, USA. tanakato@mail.nih.gov – sequence: 2 givenname: Paul surname: Scheet fullname: Scheet, Paul – sequence: 3 givenname: Betti surname: Giusti fullname: Giusti, Betti – sequence: 4 givenname: Stefania surname: Bandinelli fullname: Bandinelli, Stefania – sequence: 5 givenname: Maria Grazia surname: Piras fullname: Piras, Maria Grazia – sequence: 6 givenname: Gianluca surname: Usala fullname: Usala, Gianluca – sequence: 7 givenname: Sandra surname: Lai fullname: Lai, Sandra – sequence: 8 givenname: Antonella surname: Mulas fullname: Mulas, Antonella – sequence: 9 givenname: Anna Maria surname: Corsi fullname: Corsi, Anna Maria – sequence: 10 givenname: Anna surname: Vestrini fullname: Vestrini, Anna – sequence: 11 givenname: Francesco surname: Sofi fullname: Sofi, Francesco – sequence: 12 givenname: Anna Maria surname: Gori fullname: Gori, Anna Maria – sequence: 13 givenname: Rosanna surname: Abbate fullname: Abbate, Rosanna – sequence: 14 givenname: Jack surname: Guralnik fullname: Guralnik, Jack – sequence: 15 givenname: Andrew surname: Singleton fullname: Singleton, Andrew – sequence: 16 givenname: Goncalo R surname: Abecasis fullname: Abecasis, Goncalo R – sequence: 17 givenname: David surname: Schlessinger fullname: Schlessinger, David – sequence: 18 givenname: Manuela surname: Uda fullname: Uda, Manuela – sequence: 19 givenname: Luigi surname: Ferrucci fullname: Ferrucci, Luigi
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Snippet	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...
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SubjectTerms	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
Title	Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations
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