ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2012
Rare coding variants in ALPL are associated with low serum alkaline phosphatase and low bone mineral density.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- The Osteoporotic Fractures in Men study (MrOS): a 25-yr landmark study of skeletal health in older men.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Article
- The Benefits of Whole-Exome Sequencing in the Differential Diagnosis of Hypophosphatasia.International journal of molecular sciences · 2024Article
- Article
- Susceptibility to Low Vitamin B6 Diet-induced Gestational Diabetes Is Modulated by Strain Differences in Mice.Endocrinology · 2023Article
- Sex-specific transcriptome differences in a middle-aged frailty cohort.BMC geriatrics · 2022Article
- Young woman with hypophosphatasia: A case report.Clinical case reports · 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
- Common variants in MAEA gene contributed the susceptibility to osteoporosis in Han Chinese postmenopausal women.Journal of orthopaedic surgery and research · 2021Article
- Loss-of-function genomic variants highlight potential therapeutic targets for cardiovascular disease.Nature communications · 2020Article
- Hypophosphatasia in adolescents and adults: overview of diagnosis and treatment.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2020Review
- Phenotypic Profiling in Subjects Heterozygous for 1 of 2 Rare Variants in the Hypophosphatasia Gene (Journal of the Endocrine Society · 2020Article
- Loss-of-Function Mutations in the ALPL Gene Presenting with Adult Onset Osteoporosis and Low Serum Concentrations of Total Alkaline Phosphatase.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020Article
- ALPL mutations in adults with rheumatologic disorders and low serum alkaline phosphatase activity.Journal of bone and mineral metabolism · 2019Article
- How To Build a Bone: PHOSPHO1, Biomineralization, and Beyond.JBMR plus · 2019Review
- Genetic Contribution to Variation in Blood Calcium, Phosphorus, and Alkaline Phosphatase Activity in Pigs.Frontiers in genetics · 2019Article
- Genetic analysis of adults heterozygous for ALPL mutations.Journal of bone and mineral metabolism · 2018Article
- Mutational and biochemical findings in adults with persistent hypophosphatasemia.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2017Article
- Osteoporosis in men: findings from the Osteoporotic Fractures in Men Study (MrOS).Therapeutic advances in musculoskeletal disease · 2016Review
- Hypophosphatasia: an overview of the disease and its treatment.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2015Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Alkaline phosphatase (ALP) plays an essential role in the regulation of tissue mineralization, and its activity is highly heritable. Guided by genetic associations discovered in a murine model, we hypothesized a role for rare coding variants in determining serum ALP level and bone mineral density (BMD) in humans. We sequenced the coding regions of the ALP gene (ALPL) in men with low and normal serum ALP activity levels. Single-nucleotide ALPL variants, including 19 rare nonsynonymous variants (minor allele frequency <1%), were much more frequent among the low ALP group (33.8%) than the normal group (1.4%, p = 1 × 10(-11)). Within the low ALP group, men with a rare, nonsynonymous variant had 11.2% lower mean serum ALP (p = 3.9 × 10(-4)), 6.7% lower BMD (p = 0.03), and 11.1% higher serum phosphate (p = 0.002) than those without. In contrast, common nonsynonymous variants had no association with serum ALP, phosphate, or BMD. Multiple rare ALPL coding variants are present in the general population, and nonsynonymous coding variants may be responsible for heritable differences in mineralization and thus BMD.
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