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Vitamin D and calcium-sensing receptor polymorphisms differentially associate with resting energy expenditure in peripubertal children

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Abstract

Given that calcium metabolism is influenced by genes and is tightly linked to energy-utilizing pathways, this study evaluated the association of single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) and calcium-sensing receptor (CASR) with resting energy expenditure (REE). In 273 boys and girls, 7–12 years of age, cross-sectional REE was measured via indirect calorimetry, body composition by DXA, and dietary measures by 24-h recall. SNPs for VDR Cdx-2 (rs11568820) and CASR A986S (rs1801725) were genotyped using the Illumina Golden Gate assay. Multiple linear regression models were used to determine the association between SNPs and REE. African American carriers of the ‘A’ VDR Cdx2 allele had increased levels of REE in the overall sample, and this association was apparent among participants with an adiposity level of <25 % and 30 % body fat in males and females, respectively. For CASR, an association between carriers of the ‘A’ allele and REE was observed only in those in the upper median of calcium intake. VDR and CASR variants are associated with REE in children and are influenced by levels of calcium intake and adiposity. Our results bring awareness to mechanisms underlying the regulation of REE and biological and dietary influential factors.

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References

  1. Abrams SA, O’Brien KO, Liang LK, Stuff JE (1995) Differences in calcium absorption and kinetics between black and white girls aged 5–16 years. J Bone Miner Res 10:829–833

    Article  PubMed  CAS  Google Scholar 

  2. Arai H, Miyamoto KI, Yoshida M, Yamamoto H, Taketani Y, Morita K, Kubota M, Yoshida S, Ikeda M, Watabe F, Kanemasa Y, Takeda E (2001) The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene. J Bone Miner Res 16:1256–1264

    Article  PubMed  CAS  Google Scholar 

  3. Ashraf A, Alvarez J, Saenz K, Gower B, McCormick K, Franklin F (2009) Threshold for effects of vitamin D deficiency on glucose metabolism in obese female African-American adolescents. J Clin Endocrinol Metab 94:3200–3206

    Article  PubMed  CAS  Google Scholar 

  4. Ausili E, Rigante D, Salvaggio E, Focarelli B, Rendeli C, Ansuini V, Paolucci V, Triarico S, Martini L, Caradonna P (2012) Determinants of bone mineral density, bone mineral content, and body composition in a cohort of healthy children: influence of sex, age, puberty, and physical activity. Rheumatol Int 32(9):2737–2743

    Google Scholar 

  5. Bonilla C, Shriver MD, Parra EJ, Jones A, Fernandez JR (2004) Ancestral proportions and their association with skin pigmentation and bone mineral density in Puerto Rican women from New York City. Hum Genet 115:57–68

    Article  PubMed  Google Scholar 

  6. Brage S, Wedderkopp N, Ekelund U, Franks PW, Wareham NJ, Andersen LB, Froberg K (2004) Objectively measured physical activity correlates with indices of insulin resistance in Danish children. The European Youth Heart Study (EYHS). Int J Obes Relat Metab Disord 28:1503–1508

    Article  PubMed  CAS  Google Scholar 

  7. Braun M, Palacios C, Wigertz K, Jackman LA, Bryant RJ, McCabe LD, Martin BR, McCabe GP, Peacock M, Weaver CM (2007) Racial differences in skeletal calcium retention in adolescent girls with varied controlled calcium intakes. Am J Clin Nutr 85:1657–1663

    PubMed  CAS  Google Scholar 

  8. Casazza K, Dulin-Keita A, Gower BA, Fernandez JR (2009) Relationships between reported macronutrient intake and insulin dynamics in a multi-ethnic cohort of early pubertal children. Int J Pediatr Obes 4:249–256

    Article  PubMed  Google Scholar 

  9. Casazza K, Gower BA, Willig AL, Hunter GR, Fernandez JR (2009) Physical fitness, activity, and insulin dynamics in early pubertal children. Pediatr Exerc Sci 21:63–76

    PubMed  Google Scholar 

  10. Casazza K, Thomas O, Dulin-Keita A, Fernandez JR (2010) Adiposity and genetic admixture, but not race/ethnicity, influence bone mineral content in peripubertal children. J Bone Miner Metab 28:424–432

    Article  PubMed  Google Scholar 

  11. National Center for Health Statistics (2000) CDC Growth Charts: United States. Available from: http://www.cdc.gov/growthcharts/. Accessed 31 July 2009

  12. Coleman L, Coleman J (2002) The measurement of puberty: a review. J Adolesc 25:535–550

    Article  PubMed  Google Scholar 

  13. Fan X, Anderson EJ, Copeland PM, Borba CP, Nguyen DD, Freudenreich O, Goff DC, Henderson DC (2006) Higher fasting serum insulin is associated with increased resting energy expenditure in nondiabetic schizophrenia patients. Biol Psychiatry 60:1372–1377

    Article  PubMed  CAS  Google Scholar 

  14. Fernandez JR, Shriver MD, Beasley TM, Rafla-Demetrious N, Parra E, Albu J, Nicklas B, Ryan AS, McKeigue PM, Hoggart CL, Weinsier RL, Allison DB (2003) Association of African genetic admixture with resting metabolic rate and obesity among women. Obes Res 11:904–911

    Article  PubMed  Google Scholar 

  15. Gallagher D, Albu J, He Q, Heshka S, Boxt L, Krasnow N, Elia M (2006) Small organs with a high metabolic rate explain lower resting energy expenditure in African American than in white adults. Am J Clin Nutr 83:1062–1067

    PubMed  CAS  Google Scholar 

  16. Gimble JM, Zvonic S, Floyd ZE, Kassem M, Nuttall ME (2006) Playing with bone and fat. J Cell Biochem 98:251–266

    Article  PubMed  CAS  Google Scholar 

  17. Gower BA, Fernandez JR, Beasley TM, Shriver MD, Goran MI (2003) Using genetic admixture to explain racial differences in insulin-related phenotypes. Diabetes 52:1047–1051

    Article  PubMed  CAS  Google Scholar 

  18. Grzela T, Chudzinski W, Lasiecka Z, Niderla J, Wilczynski G, Gornicka B, Wasiutynski A, Durlik M, Boszczyk A, Brawura-Biskupski-Samaha R, Dziunycz P, Milewski L, Lazarczyk M, Lazarczyk M, Nawrot I (2006) The calcium-sensing receptor and vitamin D receptor expression in tertiary hyperparathyroidism. Int J Mol Med 17:779–783

    PubMed  CAS  Google Scholar 

  19. Hanis CL, Chakraborty R, Ferrell RE, Schull WJ (1986) Individual admixture estimates: disease associations and individual risk of diabetes and gallbladder disease among Mexican-Americans in Starr County, Texas. Am J Phys Anthropol 70:433–441

    Article  PubMed  CAS  Google Scholar 

  20. Hawkins JR, Khripin Y, Valdes AM, Weaver TA (2002) Miniaturized sealed-tube allele-specific PCR. Hum Mutat 19:543–553

    Article  PubMed  CAS  Google Scholar 

  21. Herman-Giddens ME, Slora EJ, Wasserman RC, Bourdony CJ, Bhapkar MV, Koch GG, Hasemeier CM (1997) Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings network. Pediatrics 99:505–512

    Article  PubMed  CAS  Google Scholar 

  22. Jackman LA, Millane SS, Martin BR, Wood OB, McCabe GP, Peacock M, Weaver CM (1997) Calcium retention in relation to calcium intake and postmenarcheal age in adolescent females. Am J Clin Nutr 66:327–333

    PubMed  CAS  Google Scholar 

  23. Jacobsen R, Lorenzen JK, Toubro S, Krog-Mikkelsen I, Astrup A (2005) Effect of short-term high dietary calcium intake on 24-h energy expenditure, fat oxidation, and fecal fat excretion. Int J Obes (Lond) 29:292–301

    Article  CAS  Google Scholar 

  24. Kamycheva E, Sundsfjord J, Jorde R (2004) Serum parathyroid hormone level is associated with body mass index. The 5th Tromso study. Eur J Endocrinol 151:167–172

    Article  PubMed  CAS  Google Scholar 

  25. Kapur K, Johnson T, Beckmann ND, Sehmi J, Tanaka T et al (2010) Genome-wide meta-analysis for serum calcium identifies significantly associated SNPs near the calcium-sensing receptor (CASR) gene. PLoS Genet 6:e1001035

    Article  PubMed  Google Scholar 

  26. Klimentidis YC, Divers J, Casazza K, Beasley TM, Allison DB, Fernandez JR (2011) Ancestry-informative markers on chromosomes 2, 8 and 15 are associated with insulin-related traits in a racially diverse sample of children. Hum Genomics 5:79–89

    Article  PubMed  CAS  Google Scholar 

  27. Lee WT, Jiang J (2008) Calcium requirements for Asian children and adolescents. Asia Pac J Clin Nutr 17(suppl 1):33–36

    Google Scholar 

  28. Malina RM, Bouchard C (1991) Growth, maturation, and physical activity. Human Kinetics Books, Champaign

    Google Scholar 

  29. Marshall WA, Tanner JM (1969) Variations in pattern of pubertal changes in girls. Arch Dis Child 44:291–303

    Article  PubMed  CAS  Google Scholar 

  30. Marshall WA, Tanner JM (1970) Variations in the pattern of pubertal changes in boys. Arch Dis Child 45:13–23

    Article  PubMed  CAS  Google Scholar 

  31. Melanson EL, Donahoo WT, Dong F, Ida T, Zemel MB (2005) Effect of low- and high-calcium dairy-based diets on macronutrient oxidation in humans. Obes Res 13:2102–2112

    Article  PubMed  CAS  Google Scholar 

  32. Misawa K, Fujii S, Yamazaki T, Takahashi A, Takasaki J, Yanagisawa M, Ohnishi Y, Nakamura Y, Kamatani N (2008) New correction algorithms for multiple comparisons in case-control multilocus association studies based on haplotypes and diplotype configurations. J Hum Genet 53:789–801

    Article  PubMed  Google Scholar 

  33. O’Seaghdha CM, Yang Q, Glazer NL, Leak TS, Dehghan A et al (2010) Common variants in the calcium-sensing receptor gene are associated with total serum calcium levels. Hum Mol Genet 19:4296–4303

    Article  PubMed  Google Scholar 

  34. Pacini G, Bergman RN (1986) MINMOD: a computer program to calculate insulin sensitivity and pancreatic responsivity from the frequently sampled intravenous glucose tolerance test. Comput Methods Programs Biomed 23:113–122

    Article  PubMed  CAS  Google Scholar 

  35. Park YK, Kim I, Yetley EA (1991) Characteristics of vitamin and mineral supplement products in the United States. Am J Clin Nutr 54:750–759

    PubMed  CAS  Google Scholar 

  36. Parra EJ, Kittles RA, Shriver MD (2004) Implications of correlations between skin color and genetic ancestry for biomedical research. Nat Genet 36:S54–S60

    Article  PubMed  CAS  Google Scholar 

  37. Rajakumar K, Fernstrom JD, Holick MF, Janosky JE, Greenspan SL (2008) Vitamin D status and response to Vitamin D(3) in obese vs. non-obese African American children. Obesity (Silver Spring) 16:90–95

    Article  CAS  Google Scholar 

  38. Riccardi D, Brown EM (2010) Physiology and pathophysiology of the calcium-sensing receptor in the kidney. Am J Physiol Renal Physiol 298:F485–F499

    Article  PubMed  CAS  Google Scholar 

  39. Schwartz MW, Boyko EJ, Kahn SE, Ravussin E, Bogardus C (1995) Reduced insulin secretion: an independent predictor of body weight gain. J Clin Endocrinol Metab 80:1571–1576

    Article  PubMed  CAS  Google Scholar 

  40. Snijder MB, van Dam RM, Visser M, Deeg DJ, Dekker JM, Bouter LM, Seidell JC, Lips P (2005) Adiposity in relation to vitamin D status and parathyroid hormone levels: a population-based study in older men and women. J Clin Endocrinol Metab 90:4119–4123

    Article  PubMed  CAS  Google Scholar 

  41. Teegarden D, White KM, Lyle RM, Zemel MB, Van L, Matkovic V, Craig BA, Schoeller DA (2008) Calcium and dairy product modulation of lipid utilization and energy expenditure. Obesity (Silver Spring) 16:1566–1572

    Article  CAS  Google Scholar 

  42. Tremblay A, Boule N, Doucet E, Woods SC (2005) Is the insulin resistance syndrome the price to be paid to achieve body weight stability? Int J Obes (Lond) 29:1295–1298

    Article  CAS  Google Scholar 

  43. Uitterlinden AG, Fang Y, van Meurs JB, Pols HA, van Leeuwen JP (2004) Genetics and biology of vitamin D receptor polymorphisms. Gene (Amst) 338:143–156

    Article  CAS  Google Scholar 

  44. Van LM (2009) The role of dairy foods and dietary calcium in weight management. J Am Coll Nutr 28(suppl 1):120S–129S

    Google Scholar 

  45. Watanabe RM, Steil GM, Bergman RN (1998) Critical evaluation of the combined model approach for estimation of prehepatic insulin secretion. Am J Physiol 274:E172–E183

    PubMed  CAS  Google Scholar 

  46. Weaver CM, McCabe LD, McCabe GP, Braun M, Martin BR, DiMeglio LA, Peacock M (2008) Vitamin D status and calcium metabolism in adolescent black and white girls on a range of controlled calcium intakes. J Clin Endocrinol Metab 93:3907–3914

    Article  PubMed  CAS  Google Scholar 

  47. Weyer C, Bogardus C, Pratley RE (1999) Metabolic factors contributing to increased resting metabolic rate and decreased insulin-induced thermogenesis during the development of type 2 diabetes. Diabetes 48:1607–1614

    Article  PubMed  CAS  Google Scholar 

  48. Weyer C, Snitker S, Rising R, Bogardus C, Ravussin E (1999) Determinants of energy expenditure and fuel utilization in man: effects of body composition, age, sex, ethnicity and glucose tolerance in 916 subjects. Int J Obes Relat Metab Disord 23:715–722

    Article  PubMed  CAS  Google Scholar 

  49. Williams DP, Going SB, Lohman TG, Harsha DW, Srinivasan SR, Webber LS, Berenson GS (1992) Body fatness and risk for elevated blood pressure, total cholesterol, and serum lipoprotein ratios in children and adolescents. Am J Public Health 82:358–363

    Article  PubMed  CAS  Google Scholar 

  50. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF (2000) Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 72:690–693

    PubMed  CAS  Google Scholar 

  51. Yamamoto H, Miyamoto K, Li B, Taketani Y, Kitano M, Inoue Y, Morita K, Pike JW, Takeda E (1999) The caudal-related homeodomain protein Cdx-2 regulates vitamin D receptor gene expression in the small intestine. J Bone Miner Res 14:240–247

    Article  PubMed  CAS  Google Scholar 

  52. Zemel MB (2003) Role of dietary calcium and dairy products in modulating adiposity. Lipids 38:139–146

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This research was supported by National Institutes of Health grants R01DK 067426, R25CA47888, UL1TR000165, T32DK007545, and P30-DK56336. L.J.H., K.C., and J.R.F. contributed to conception and design, acquisition of data, analysis and interpretation of data, and drafting of the manuscript. A.P.A., S.R., J.A., M.S.B., and T.M.B. contributed to analysis and interpretation of data and drafting of the manuscript.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Nutrition Sciences, University of Alabama at Birmingham, Webb 445, 1720 Second Ave South, Birmingham, AL, 35294-3360, USA

    Lynae J. Hanks, Krista Casazza, Jamy Ard & Jose R. Fernandez

  2. Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA

    Ambika P. Ashraf

  3. Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA

    Sasanka Ramanadham

  4. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA

    Molly S. Bray

  5. Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA

    T. Mark Beasley & Jose R. Fernandez

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  1. Lynae J. Hanks
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  2. Krista Casazza
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Correspondence to Lynae J. Hanks.

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Hanks, L.J., Casazza, K., Ashraf, A.P. et al. Vitamin D and calcium-sensing receptor polymorphisms differentially associate with resting energy expenditure in peripubertal children. J Bone Miner Metab 31, 695–702 (2013). https://doi.org/10.1007/s00774-013-0454-9

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  • DOI: https://doi.org/10.1007/s00774-013-0454-9

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