ArticleThe Journal of nutrition2015
Common Variants at Putative Regulatory Sites of the Tissue Nonspecific Alkaline Phosphatase Gene Influence Circulating Pyridoxal 5'-Phosphate Concentration in Healthy Adults.
Article in The Journal of nutrition, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Metabolomics and Human Health: Progress, Insights, Challenges and the Concept of a Healthy Metabolome.Biomolecules · 2026Review
- Article
- Factors influencing vitamin B6 status in domestic cats: age, disease, and body condition score.Scientific reports · 2024Article
- Susceptibility to Low Vitamin B6 Diet-induced Gestational Diabetes Is Modulated by Strain Differences in Mice.Endocrinology · 2023Article
- Scientific opinion on the tolerable upper intake level for vitamin B6.EFSA journal. European Food Safety Authority · 2023Article
- Investigating Genetic Determinants of Plasma Inositol Status in Adult Humans.The Journal of nutrition · 2022Article
- Polymorphic variants of alkaline phosphatase gene correlate with clinical signs of adult hypophosphatasia?Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2021Article
- Genotype-Phenotype Associations in 72 Adults with Suspected ALPL-Associated Hypophosphatasia.Calcified tissue international · 2021Article
- Assessing the genetic association between vitamin B6 metabolism and genetic generalized epilepsy.Molecular genetics and metabolism reports · 2019Article
- ComPaSS-GWAS: A method to reduce type I error in genome-wide association studies when replication data are not available.Genetic epidemiology · 2019Article
- The Alkaline Phosphatase (ALPL) Locus Is Associated with B6 Vitamer Levels in CSF and Plasma.Genes · 2018Article
- The 677C→T variant of MTHFR is the major genetic modifier of biomarkers of folate status in a young, healthy Irish population.The American journal of clinical nutrition · 2018Article
- Suboptimal maternal and cord plasma pyridoxal 5' phosphate concentrations are uncommon in a cohort of Canadian pregnant women and newborn infants.Maternal & child nutrition · 2018Article
- Prevalence and Predictors of Low Vitamin B6 Status in Healthy Young Adult Women in Metro Vancouver.Nutrients · 2016Article
- A Common Polymorphism in HIBCH Influences Methylmalonic Acid Concentrations in Blood Independently of Cobalamin.American journal of human genetics · 2016Article
- Direct and Functional Biomarkers of Vitamin B6 Status.Annual review of nutrition · 2015Review
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 3 countries.
Funding
Abstract
backgroundVitamin B-6 interconversion enzymes are important for supplying pyridoxal 5'-phosphate (PLP), the co-enzyme form, to tissues. Variants in the genes for these enzymes [tissue nonspecific alkaline phosphatase (ALPL), pyridoxamine 5'-phosphate oxidase, pyridoxal kinase, and pyridoxal phosphatase] could affect enzyme function and vitamin B-6 status.
objectivesWe tested whether single-nucleotide polymorphisms (SNPs) in these genes influence vitamin B-6 status markers [plasma PLP, pyridoxal (PL), and 4-pyridoxic acid (PA)], and explored potential functional effects of the SNPs.
methodsStudy subjects were young, healthy adults from Ireland (n = 2345). We measured plasma PLP, PL, and PA with liquid chromatography-tandem mass spectrometry and genotyped 66 tag SNPs in the 4 genes. We tested for associations with single SNPs in candidate genes and also performed genome-wide association study (GWAS) and gene-based analyses.
resultsSeventeen SNPs in ALPL were associated with altered plasma PLP in candidate gene analyses (P < 1.89 × 10(-4)). In the GWAS, 5 additional ALPL SNPs were associated with altered plasma PLP (P < 5.0 × 10(-8)). Gene-based analyses that used the functional linear model β-spline (P = 4.04 × 10(-15)) and Fourier spline (P = 5.87 × 10(-15)) methods also showed associations between ALPL and altered plasma PLP. No SNPs in other genes were associated with plasma PLP. The association of the minor CC genotype of 1 ALPL SNP, rs1256341, with reduced ALPL expression in the HapMap Northern European ancestry population is consistent with the positive association between the CC genotype and plasma PLP in our study (P = 0.008). No SNP was associated with altered plasma PL or PA.
conclusionsIn healthy adults, common variants in ALPL influence plasma PLP concentration, the most frequently used biomarker for vitamin B-6 status. Whether these associations are indicative of functional changes in vitamin B-6 status requires more investigation.
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