Precision Vitamin D Therapy in Pediatrics: Interplay of Genetic Architecture and Environmental Factors
Keywords:
Precision Vitamin D Therapy, , genetic factors, Environmental FactorsAbstract
Vitamin D supplementation in children remains largely based on generalized age-related recommendations, despite substantial variability in individual requirements and treatment response. This variability reflects interactions between genetic, physiological, and environmental factors. Genetic variants involving DHCR7, CYP2R1, GC, and CYP24A1 can influence vitamin D synthesis, hydroxylation, transport, and catabolism, thereby affecting circulating 25-hydroxyvitamin D [25(OH)D] concentrations and response to supplementation. Rare pathogenic variants, particularly in CYP2R1, may cause refractory deficiency or rickets requiring alternative therapeutic approaches. Important non-genetic modifiers include obesity, skin pigmentation, latitude, season, ultraviolet-B exposure, and maternal vitamin D status during pregnancy. These factors challenge a universal age-based dosing strategy and support a more individualized approach. In routine practice, vitamin D dosing can be refined according to body weight or adiposity, environmental and seasonal exposure, and follow-up measurement of serum 25(OH)D. Genetic evaluation may be considered in children with persistent or recurrent deficiency despite adequate adherence and appropriately adjusted supplementation. Precision-guided vitamin D therapy may improve the effectiveness and sustainability of supplementation in pediatric populations.
References
1. Nguyen TT, Nojiri K, Kurokawa T, Sawada T, Kanemoto Y, Kato S. Vitamin D Receptor Signaling and Ligand Modulation: Molecular Mechanisms and Therapeutic Implications. Int J Mol Sci. 2026;27(5):2396. doi: 10.3390/ijms27052396.
2. Wang TJ, Zhang F, Richards JB, et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 2010;376(9736):180-188. doi:10.1016/S0140-6736(10)60588-0.
3. Munns CF, Shaw N, Kiely M, et al. Global consensus recommendations on prevention and management of nutritional rickets. J Clin Endocrinol Metab. 2016;101(2):394-415. doi:10.1210/jc.2015-2175.
4. Thacher TD, Fischer PR, Singh RJ, Roizen J, Levine MA. CYP2R1 mutations impair generation of 25-hydroxyvitamin D and cause an atypical form of vitamin D deficiency. J Clin Endocrinol Metab. 2015;100(7):E1005-E1013. doi:10.1210/jc.2015-1746.
5. Drincic AT, Armas LA, van Diest EE, Heaney RP. Volumetric dilution, rather than sequestration best explains the low vitamin D status of obesity. Obesity (Silver Spring). 2012;20(7):1444-1448. doi:10.1038/oby.2011.404.
6. Cooper C, Harvey NC, Bishop NJ, et al. Maternal gestational vitamin D supplementation and offspring bone health (MAVIDOS): a multicentre, double-blind, randomised placebo-controlled trial. Lancet Diabetes Endocrinol. 2016;4(5):393-402. doi:10.1016/S2213-8587(16)00044-9.
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