Skip to main navigation menu Skip to main content Skip to site footer
##common.pageHeaderLogo.altText##

Original article

Vol. 142 No. 2930 (2012)

The GC, CYP2R1 and DHCR7 genes are associated with vitamin D levels in northeastern Han Chinese children

  • Yuling Zhang
  • Xi Wang
  • Ye Liu
  • Hui Qu
  • Shuqiang Qu
  • Wei Wang
  • Lihong Ren
DOI
https://doi.org/10.4414/smw.2012.13636
Cite this as:
Swiss Med Wkly. 2012;142:w13636
Published
15.07.2012

Summary

Vitamin D deficiency is associated with risk in several diseases. Vitamin D status has high heritability, yet the genetic epidemiology of vitamin D or its metabolites has not been well studied. Our objective was to identify the relationship among three vitamin D-related genes (GC, CYP2R1 and DHCR7/NADSYN1) and the levels of 25(OH)D in northeastern Han Chinese children. A total of 506 northeastern Han Chinese children were enrolled in this study. Linear regression was used to examine the impact of 12 SNPs on 25(OH)D concentrations after adjustment for age, gender, BMI and regular usage of vitamin D, and Bonferroni’s method was adopted for multiple corrections. The two SNPs in GC (rs222020, rs2298849), four SNPs in CYP2R1 (rs10741657, rs10766197, rs12794714 and rs1562902) and two SNPs in DHCR7/NADSYN1 (rs3829251, rs12785878) were significantly associated with plasma 25(OH)D concentrations under both additive and recessive models (P <0.05). The genotypes of the CYP2R1rs2060793 polymorphism showed positive association with serum 25(OH)D status under all of the three genetic models even after correction for multiple comparison. This population-based study was the first to confirm the strong effects of the GC, CYP2R1 and DHCR7/NADSYN1 loci on circulating 25(OH)D concentrations in northeastern Han Chinese children.

References

  1. Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev. 2008;29:726–76.
  2. Melamed ML, Astor B, Michos ED, Hostetter TH, Powe NR, Muntner P. 25-hydroxyvitamin D levels, race, and the progression of kidney disease. J Am Soc Nephrol. 2009;20:2631–9.
  3. Borkar VV, Devidayal, Verma S, Bhalla AK. Low levels of vitamin D in North Indian children with newly diagnosed type 1 diabetes. Pediatric diabetes. 2010;11:345–50.
  4. Kilkkinen A, Knekt P, Aro A, Rissanen H, Marniemi J, Heliovaara M, et al. Vitamin D status and the risk of cardiovascular disease death. Am J Epidemiol. 2009;170:1032–9.
  5. Bosse Y, Lemire M, Poon AH, Daley D, He JQ, Sandford A, et al. Asthma and genes encoding components of the vitamin D pathway. Respiratory research. 2009;10:98.
  6. Mikhak B, Hunter DJ, Spiegelman D, Platz EA, Hollis BW, Giovannucci E. Vitamin D receptor (VDR) gene polymorphisms and haplotypes, interactions with plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and prostate cancer risk. The Prostate. 2007;67:911–23.
  7. Heist RS, Zhou W, Wang Z, Liu G, Neuberg D, Su L, et al. Circulating 25-hydroxyvitamin D, VDR polymorphisms, and survival in advanced non-small-cell lung cancer. J Clin Oncol. 2008;26:5596–602.
  8. Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr. 2005;135:317–22.
  9. Shea MK, Benjamin EJ, Dupuis J, Massaro JM, Jacques PF, D’Agostino RB, Sr., et al. Genetic and non-genetic correlates of vitamins K and D. Eur J Clin Nutr. 2009;63:458–64.
  10. Kurylowicz A, Ramos-Lopez E, Bednarczuk T, Badenhoop K. Vitamin D-binding protein (DBP) gene polymorphism is associated with Graves’ disease and the vitamin D status in a Polish population study. Exp Clin Endocrinol Diabetes. 2006;114:329–35.
  11. Ramos-Lopez E, Bruck P, Jansen T, Herwig J, Badenhoop K. CYP2R1 (vitamin D 25-hydroxylase) gene is associated with susceptibility to type 1 diabetes and vitamin D levels in Germans. Diabetes/metabolism research and reviews. 2007;23:631–6.
  12. Wang TJ, Zhang F, Richards JB, Kestenbaum B, van Meurs JB, Berry D, et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 2010;376:180–8.
  13. Ahn J, Albanes D, Berndt SI, Peters U, Chatterjee N, Freedman ND, et al. Vitamin D-related genes, serum vitamin D concentrations and prostate cancer risk. Carcinogenesis. 2009;30:769–76.
  14. Ahn J, Yu K, Stolzenberg-Solomon R, Simon KC, McCullough ML, Gallicchio L, et al. Genome-wide association study of circulating vitamin D levels. Human molecular genetics. 2010;19:2739–45.
  15. Gordon CM, DePeter KC, Feldman HA, Grace E, Emans SJ. Prevalence of vitamin D deficiency among healthy adolescents. Arch Pediatr Adolesc Med. 2004;158:531–7.
  16. Sullivan SS, Rosen CJ, Halteman WA, Chen TC, Holick MF. Adolescent girls in Maine are at risk for vitamin D insufficiency. J Ame Diet Assoc. 2005;105:971–4.
  17. Nesby-O’Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis BW, Looker AC, et al. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988–1994. Am J Clin Nutr. 2002;76:187–92.
  18. Abrams SA, Griffin IJ, Hawthorne KM, Chen Z, Gunn SK, Wilde M, et al. Vitamin D receptor Fok1 polymorphisms affect calcium absorption, kinetics, and bone mineralization rates during puberty. J Bone Miner Res. 2005;20:945–53.
  19. Ames SK, Ellis KJ, Gunn SK, Copeland KC, Abrams SA. Vitamin D receptor gene Fok1 polymorphism predicts calcium absorption and bone mineral density in children. J Bone Miner Res. 1999;14:740–6.
  20. Gong YG, Li YN, Zhang WH, Liu LJ, Kang XG. Correlation between vitamin D receptor genetic polymorphism and 25-hydroxyvitamin D3 in vitamin D deficiency rickets. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics. 2010;12:544–6.
  21. Speeckaert M, Huang G, Delanghe JR, Taes YE. Biological and clinical aspects of the vitamin D binding protein (Gc-globulin) and its polymorphism. Clinica chimica acta; international journal of clinical chemistry. 2006;372:33–42.
  22. Abbas S, Linseisen J, Slanger T, Kropp S, Mutschelknauss EJ, Flesch-Janys D, et al. 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. 2008;17:1339–43.
  23. Sinotte M, Diorio C, Berube S, Pollak M, Brisson J. Genetic polymorphisms of the vitamin D binding protein and plasma concentrations of 25-hydroxyvitamin D in premenopausal women. Am J Clin Nutr. 2009;89:634–40.
  24. Fu L, Yun F, Oczak M, Wong BY, Vieth R, Cole DE. Common genetic variants of the vitamin D binding protein (DBP) predict differences in response of serum 25-hydroxyvitamin D [25(OH)D] to vitamin D supplementation. Clin Biochem. 2009;42:1174–7.
  25. Fang Y, van Meurs JB, Arp P, van Leeuwen JP, Hofman A, Pols HA, et al. Vitamin D binding protein genotype and osteoporosis. Calcified tissue international. 2009;85:85–93.
  26. Bu FX, Armas L, Lappe J, Zhou Y, Gao G, Wang HW, et al. Comprehensive association analysis of nine candidate genes with serum 25-hydroxy vitamin D levels among healthy Caucasian subjects. Hum Genet. 2010;128:549–56.
  27. Shinkyo R, Sakaki T, Kamakura M, Ohta M, Inouye K. Metabolism of vitamin D by human microsomal CYP2R1. Biochem Biophys Res Comm. 2004;324:451–7.
  28. Wjst M, Altmuller J, Faus-Kessler T, Braig C, Bahnweg M, Andre E. Asthma families show transmission disequilibrium of gene variants in the vitamin D metabolism and signalling pathway. Respiratory research. 2006;7:60.
  29. Cooper JD, Smyth DJ, Walker NM, Stevens H, Burren OS, Wallace C, et al. Inherited variation in vitamin D genes is associated with predisposition to autoimmune disease type 1 diabetes. Diabetes. 2011;60:1624–31.