Genetic variants modify the associations of concentrations of methylmalonic acid, vitamin B-12, vitamin B-6, and folate with bone mineral density.
B vitamins
DXA
QCT
bone mineral density
genetic polymorphism
Journal
The American journal of clinical nutrition
ISSN: 1938-3207
Titre abrégé: Am J Clin Nutr
Pays: United States
ID NLM: 0376027
Informations de publication
Date de publication:
02 08 2021
02 08 2021
Historique:
received:
14
04
2020
accepted:
05
03
2021
pubmed:
9
5
2021
medline:
2
9
2021
entrez:
8
5
2021
Statut:
ppublish
Résumé
Elevated plasma homocysteine has been found to be associated with an increased risk of osteoporosis, especially hip and vertebral fractures. The plasma concentration of homocysteine is dependent on the activities of several B vitamin-dependent enzymes, such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), and cystathionine β-synthase (CBS). We investigated whether genetic variants in some of the genes involved in 1 carbon metabolism modify the association of B vitamin-related measures with bone mineral density (BMD) and strength. We measured several B vitamins and biomarkers in participants of the Framingham Offspring Study, and performed analyses of methylmalonic acid (MMA) continuously and <210 nmol/L; pyridoxal-5'-phosphate; vitamin B-12 continuously and ≥258 pmol/L; and folate. The outcomes of interest included areal and volumetric BMD, measured by DXA and quantitative computed tomography (QCT), respectively. We evaluated associations between the bone measures and interactions of single nucleotide polymorphism with a B vitamin or biomarker in Framingham participants (n = 4310 for DXA and n = 3127 for QCT). For analysis of DXA, we validated the association results in the B-PROOF cohort (n = 1072). Bonferroni-corrected locus-wide significant thresholds were defined to account for multiple testing. The interactions between rs2274976 and vitamin B-12 and rs34671784 and MMA <210 nmol/L were associated with lumbar spine BMD, and the interaction between rs6586281 and vitamin B-12 ≥258 pmol/L was associated with femoral neck BMD. For QCT-derived traits, 62 interactions between genetic variants and B vitamins and biomarkers were identified. Some genetic variants in the 1-carbon methylation pathway modify the association of B vitamin and biomarker concentrations with bone density and strength. These interactions require further replication and functional validation for a mechanistic understanding of the role of the 1-carbon metabolism pathway on BMD and risks of fracture.
Sections du résumé
BACKGROUND
Elevated plasma homocysteine has been found to be associated with an increased risk of osteoporosis, especially hip and vertebral fractures. The plasma concentration of homocysteine is dependent on the activities of several B vitamin-dependent enzymes, such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), and cystathionine β-synthase (CBS).
OBJECTIVES
We investigated whether genetic variants in some of the genes involved in 1 carbon metabolism modify the association of B vitamin-related measures with bone mineral density (BMD) and strength.
METHODS
We measured several B vitamins and biomarkers in participants of the Framingham Offspring Study, and performed analyses of methylmalonic acid (MMA) continuously and <210 nmol/L; pyridoxal-5'-phosphate; vitamin B-12 continuously and ≥258 pmol/L; and folate. The outcomes of interest included areal and volumetric BMD, measured by DXA and quantitative computed tomography (QCT), respectively. We evaluated associations between the bone measures and interactions of single nucleotide polymorphism with a B vitamin or biomarker in Framingham participants (n = 4310 for DXA and n = 3127 for QCT). For analysis of DXA, we validated the association results in the B-PROOF cohort (n = 1072). Bonferroni-corrected locus-wide significant thresholds were defined to account for multiple testing.
RESULTS
The interactions between rs2274976 and vitamin B-12 and rs34671784 and MMA <210 nmol/L were associated with lumbar spine BMD, and the interaction between rs6586281 and vitamin B-12 ≥258 pmol/L was associated with femoral neck BMD. For QCT-derived traits, 62 interactions between genetic variants and B vitamins and biomarkers were identified.
CONCLUSIONS
Some genetic variants in the 1-carbon methylation pathway modify the association of B vitamin and biomarker concentrations with bone density and strength. These interactions require further replication and functional validation for a mechanistic understanding of the role of the 1-carbon metabolism pathway on BMD and risks of fracture.
Identifiants
pubmed: 33964857
pii: S0002-9165(22)00372-0
doi: 10.1093/ajcn/nqab093
pmc: PMC8326042
doi:
Substances chimiques
Vitamin B Complex
12001-76-2
Vitamin B 6
8059-24-3
Methylmalonic Acid
8LL8S712J7
Folic Acid
935E97BOY8
Vitamin B 12
P6YC3EG204
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
578-587Subventions
Organisme : NHLBI NIH HHS
ID : HHSN268201500001C
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR072199
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR041398
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01-HC-25195
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201500001I
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR041398)
Pays : United States
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.
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