Skip to main content Accessibility help
×
Home

Common genetic variants are associated with lower serum 25-hydroxyvitamin D concentrations across the year among children at northern latitudes

  • Rikke A. Petersen (a1) (a2), Lesli H. Larsen (a2), Camilla T. Damsgaard (a2), Louise B. Sørensen (a2), Mads F. Hjorth (a2), Rikke Andersen (a3), Inge Tetens (a3), Henrik Krarup (a4), Christian Ritz (a2), Arne Astrup (a2), Kim F. Michaelsen (a2) and Christian Mølgaard (a2)...

Abstract

In a longitudinal study including 642 healthy 8–11-year-old Danish children, we investigated associations between vitamin D dependent SNP and serum 25-hydroxyvitamin D (25(OH)D) concentrations across a school year (August–June). Serum 25(OH)D was measured three times for every child, which approximated measurements in three seasons (autumn, winter, spring). Dietary and supplement intake, physical activity, BMI and parathyroid hormone were likewise measured at each time point. In all, eleven SNP in four vitamin D-related genes: Cytochrome P450 subfamily IIR1 (CYP2R1); 7-dehydrocholesterol reductase/nicotinamide adenine dinucleotide synthetase-1(DHCR7/NADSYN1); group-specific complement (GC); and vitamin D receptor were genotyped. We found minor alleles of CYP2R1 rs10500804, and of GC rs4588 and rs7041 to be associated with lower serum 25(OH)D concentrations across the three seasons (all P<0·01), with estimated 25(OH)D differences of −5·8 to −10·6 nmol/l from major to minor alleles homozygosity. In contrast, minor alleles homozygosity of rs10741657 and rs1562902 in CYP2R1 was associated with higher serum 25(OH)D concentrations compared with major alleles homozygosity (all P<0·001). Interestingly, the association between season and serum 25(OH)D concentrations was modified by GC rs7041 (P interaction=0·044), observed as absence of increase in serum 25(OH)D from winter to spring among children with minor alleles homozygous genotypes compared with the two other genotypes of rs7041 (P<0·001). Our results suggest that common genetic variants are associated with lower serum 25(OH)D concentrations across a school year. Potentially due to modified serum 25(OH)D response to UVB sunlight exposure. Further confirmation and paediatric studies investigating vitamin D-related health outcomes of these genotypic differences are needed.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Common genetic variants are associated with lower serum 25-hydroxyvitamin D concentrations across the year among children at northern latitudes
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Common genetic variants are associated with lower serum 25-hydroxyvitamin D concentrations across the year among children at northern latitudes
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Common genetic variants are associated with lower serum 25-hydroxyvitamin D concentrations across the year among children at northern latitudes
      Available formats
      ×

Copyright

Corresponding author

* Corresponding author: R. A. Petersen, email riap@ucl.dk

References

Hide All
1. Molgaard, C, Thomsen, BL & Michaelsen, KF (1999) Whole body bone mineral accretion in healthy children and adolescents. Arch Dis Child 81, 1015.
2. Williams, DM, Fraser, A, Sayers, A, et al. (2012) Associations of 25-hydroxyvitamin D2 and D3 with cardiovascular risk factors in childhood: cross-sectional findings from the Avon Longitudinal Study of Parents and Children. J Clin Endocrinol Metab 97, 15631571.
3. Pacifico, L, Anania, C, Osborn, JF, et al. (2011) Low 25(OH)D3 levels are associated with total adiposity, metabolic syndrome, and hypertension in Caucasian children and adolescents. Eur J Endocrinol 165, 603611.
4. Olson, ML, Maalouf, NM, Oden, JD, et al. (2012) Vitamin D deficiency in obese children and its relationship to glucose homeostasis. J Clin Endocrinol Metab 97, 279285.
5. Petersen, RA, Dalskov, SM, Sorensen, LB, et al. (2015) Vitamin D status is associated with cardiometabolic markers in 8-11-year-old children, independently of body fat and physical activity. Br J Nutr 114, 16471655.
6. Holick, MF (2004) Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr 80, Suppl. 6, 1678S1688S.
7. Webb, AR, Kline, L & Holick, MF (1988) Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab 67, 373378.
8. Kimlin, MG (2008) Geographic location and vitamin D synthesis. Mol Aspects Med 29, 453461.
9. Andersen, R, Brot, C, Jakobsen, J, et al. (2013) Seasonal changes in vitamin D status among Danish adolescent girls and elderly women: the influence of sun exposure and vitamin D intake. Eur J Clin Nutr 67, 270274.
10. Eriksson, S & Strandvik, B (2010) Vitamin D status in healthy children in Sweden still satisfactory. Changed supplementation and new knowledge motivation for further studies. Lakartidningen 107, 24742477. English abstract: http://ltarkiv.lakartidningen.se/artNo38693
11. Ohlund, I, Silfverdal, SA, Hernell, O, et al. (2012) Serum 25-hydroxyvitamin D levels in pre-school children in northern Sweden are inadequate after the summer season and diminishes further during winter. J Pediatr Gastroenterol Nutr 56, 551555.
12. Madsen, KH, Rasmussen, LB, Andersen, R, et al. (2013) Randomized controlled trial of the effects of vitamin D-fortified milk and bread on serum 25-hydroxyvitamin D concentrations in families in Denmark during winter: the VitmaD study. Am J Clin Nutr 98, 374382.
13. Petersen, RA, Damsgaard, CT, Dalskov, SM, et al. (2015) Vitamin D status and its determinants during autumn in children at northern latitudes: a cross-sectional analysis from the optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study. Br J Nutr 115, 239250.
14. Berry, D & Hypponen, E (2011) Determinants of vitamin D status: focus on genetic variations. Curr Opin Nephrol Hypertens 20, 331336.
15. Wang, TJ, Zhang, F, Richards, JB, et al. (2010) Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet 376, 180188.
16. McGrath, JJ, Saha, S, Burne, TH, et al. (2010) A systematic review of the association between common single nucleotide polymorphisms and 25-hydroxyvitamin D concentrations. J Steroid Biochem Mol Biol 121, 471477.
17. Pekkinen, M, Saarnio, E, Viljakainen, HT, et al. (2014) Vitamin D binding protein genotype is associated with serum 25-hydroxyvitamin D and PTH concentrations, as well as bone health in children and adolescents in Finland. PLOS ONE 9, e87292.
18. Nissen, J, Rasmussen, LB, Ravn-Haren, G, et al. (2014) Common variants in CYP2R1 and GC genes predict vitamin D concentrations in healthy Danish children and adults. PLOS ONE 9, e89907.
19. Nissen, J, Vogel, U, Ravn-Haren, G, et al. (2014) Real-life use of vitamin D3-fortified bread and milk during a winter season: the effects of CYP2R1 and GC genes on 25-hydroxyvitamin D concentrations in Danish families, the VitmaD study. Genes Nutr 9, 413.
20. Snellman, G, Melhus, H, Gedeborg, R, et al. (2009) Seasonal genetic influence on serum 25-hydroxyvitamin D levels: a twin study. PLoS ONE 4, e7747.
21. Gozdzik, A, Zhu, J, Wong, BY, et al. (2011) Association of vitamin D binding protein (VDBP) polymorphisms and serum 25(OH)D concentrations in a sample of young Canadian adults of different ancestry. J Steroid Biochem Mol Biol 127, 405412.
22. Engelman, CD, Meyers, KJ, Iyengar, SK, et al. (2013) Vitamin D intake and season modify the effects of the GC and CYP2R1 genes on 25-hydroxyvitamin D concentrations. J Nutr 143, 1726.
23. Damsgaard, CT, Dalskov, SM, Petersen, RA, et al. (2012) Design of the OPUS School Meal Study: a randomised controlled trial assessing the impact of serving school meals based on the New Nordic Diet. Scand J Public Health 40, 693703.
24. Petersen, RA, Damsgaard, CT, Dalskov, SM, et al. (2015) Effects of school meals with weekly fish servings on vitamin D status in Danish children: secondary outcomes from the OPUS (Optimal well-being, development and health for Danish children through a healthy New Nordic Diet) School Meal Study. J Nutr Sci 4, 110.
25. Statistics Denmark (2011) Immigrants and their descendants. https://www.dst.dk/da/Statistik/emner/indvandrere-og-efterkommere/indvandrere-og-efterkommere?tab=dok (accessed February 2012).
26. Morris, N & Udry, JR (1980) Validation of a self-administered instrument to assess stage of adolescent development. J Youth Adolesc 9, 271280.
27. Biltoft-Jensen, A, Trolle, E, Christensen, T, et al. (2014) WebDASC: a web-based dietary assessment software for 8-11-year-old Danish children. J Hum Nutr Diet 27, Suppl. 1, 4353.
28. Pedersen, A, Fagt, S, Groth, M, et al. (2010) Danskernes kostvaner 2003–2008 (Dietary habits in Denmark 2003–2008) [in Danish]. Søborg: DTU Fødevareinstituttet, Division of Nutrition, National Food Institute, Technical University Denmark.
29. Biltoft-Jensen, A, Hjorth, MF, Trolle, E, et al. (2013) Comparison of estimated energy intake using Web-based Dietary Assessment Software with accelerometer-determined energy expenditure in children. Food Nutr Res 57, 10.3402/fnr.v57i0.21434.
30. Biltoft-Jensen, A, Bysted, A, Trolle, E, et al. (2013) Evaluation of Web-based Dietary Assessment Software for Children: comparing reported fruit, juice and vegetable intakes with plasma carotenoid concentration and school lunch observations. Br J Nutr 110, 186195.
31. Henry, CJ (2005) Basal metabolic rate studies in humans: measurement and development of new equations. Public Health Nutr 8, 11331152.
32. Black, AE (2000) The sensitivity and specificity of the Goldberg cut-off for EI:BMR for identifying diet reports of poor validity. Eur J Clin Nutr 54, 395404.
33. Hjorth, MF, Chaput, JP, Michaelsen, K, et al. (2013) Seasonal variation in objectively measured physical activity, sedentary time, cardio-respiratory fitness and sleep duration among 8-11-year-old Danish children: a repeated-measures study. BMC Public Health 13, 808.
34. World Health Organization (WHO) (2012) WHO AnthroPlus Macros for STATA. http://www.who.int/growthref/tools/en/ (accessed February 2012).
35. Carter, GD, Berry, JL, Gunter, E, et al. (2010) Proficiency testing of 25-hydroxyvitamin D (25-OHD) assays. J Steroid Biochem Mol Biol 121, 176179.
36. Ahn, J, Yu, K, Stolzenberg-Solomon, R, et al. (2010) Genome-wide association study of circulating vitamin D levels. Hum Mol Genet 19, 27392745.
37. Zhang, Y, Wang, X, Liu, Y, et al. (2012) The GC, CYP2R1 and DHCR7 genes are associated with vitamin D levels in northeastern Han Chinese children. Swiss Med Wkly 142, 16.
38. Rodriguez, S, Gaunt, TR & Day, IN (2009) Hardy-Weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies. Am J Epidemiol 169, 505514.
39. Abbas, S, Linseisen, J, Slanger, T, et al. (2008) The Gc2 allele of the vitamin D binding protein is associated with a decreased postmenopausal breast cancer risk, independent of the vitamin D status. Cancer Epidemiol Biomarkers Prev 17, 13391343.
40. Lauridsen, AL, Vestergaard, P, Hermann, AP, et al. (2004) Female premenopausal fracture risk is associated with gc phenotype. J Bone Miner Res 19, 875881.
41. Cole, TJ, Flegal, KM, Nicholls, D, et al. (2007) Body mass index cut offs to define thinness in children and adolescents: international survey. BMJ 335, 194.
42. Cole, TJ, Bellizzi, MC, Flegal, KM, et al. (2000) Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 320, 12401243.
43. Braegger, C, Campoy, C, Colomb, V, et al. (2013) Vitamin D in the healthy European paediatric population. J Pediatr Gastroenterol Nutr 56, 692701.
44. Ross, AC, Manson, JE, Abrams, SA, et al. (2011) The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 96, 5358.
45. Powe, CE, Evans, MK, Wenger, J, et al. (2013) Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N Engl J Med 369, 19912000.
46. Sollid, ST, Hutchinson, MY, Fuskevag, OM, et al. (2016) Large individual differences in serum 25-hydroxyvitamin D response to vitamin D supplementation: effects of genetic factors, body mass index, and baseline concentration. Results from a randomized controlled trial. Horm Metab Res 48, 2734.
47. Nissen, J, Vogel, U, Ravn-Haren, G, et al. (2015) Common variants in CYP2R1 and GC genes are both determinants of serum 25-hydroxyvitamin D concentrations after UVB irradiation and after consumption of vitamin D(3)-fortified bread and milk during winter in Denmark. Am J Clin Nutr 101, 218227.
48. Sollid, ST, Hutchinson, MY, Berg, V, et al. (2016) Effects of vitamin D binding protein phenotypes and vitamin D supplementation on serum total 25(OH)D and directly measured free 25(OH)D. Eur J Endocrinol 174, 445452.
49. Denburg, MR, Hoofnagle, AN, Sayed, S, et al. (2016) Comparison of two ELISA methods and mass spectrometry for measurement of vitamin D-binding protein: implications for the assessment of bioavailable vitamin D concentrations across genotypes. J Bone Miner Res 31, 11281136.

Keywords

Related content

Powered by UNSILO
Type Description Title
WORD
Supplementary materials

Petersen supplementary material
Tables S1-S5

 Word (34 KB)
34 KB

Common genetic variants are associated with lower serum 25-hydroxyvitamin D concentrations across the year among children at northern latitudes

  • Rikke A. Petersen (a1) (a2), Lesli H. Larsen (a2), Camilla T. Damsgaard (a2), Louise B. Sørensen (a2), Mads F. Hjorth (a2), Rikke Andersen (a3), Inge Tetens (a3), Henrik Krarup (a4), Christian Ritz (a2), Arne Astrup (a2), Kim F. Michaelsen (a2) and Christian Mølgaard (a2)...

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.