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Variability of Osteocalcin Status in Chinese Holstein Cattle: Do Phylogeny, Vitamin D or Gene Polymorphisms Matter?

  • Ferreri, Miro (College of Veterinary Medicine, China Agricultural University) ;
  • Gao, Jian (College of Veterinary Medicine, China Agricultural University) ;
  • Ren, Gaixian (College of Veterinary Medicine, China Agricultural University) ;
  • Chen, Liben (College of Veterinary Medicine, China Agricultural University) ;
  • Su, Jingliang (College of Veterinary Medicine, China Agricultural University) ;
  • Han, Bo (College of Veterinary Medicine, China Agricultural University)
  • Received : 2010.04.29
  • Accepted : 2010.07.20
  • Published : 2011.02.01

Abstract

Osteocalcin (OC), a marker of bone turnover, displays patterns in relation to physiological and genetic factors. Here, we present an association study in a population of Chinese Holstein cattle (n = 24) with OC serum concentration as a phenotypic trait. We hypothesised that OC status is associated with phylogeny, vitamin D serum level and single nucleotide polymorphisms (SNPs). Mitochondrial DNA (mtDNA) was used as an unlinked marker to examine phylogeny and linkage to measured phenotypic traits of vitamin D and OC status. Following an association study with OC serum variability as the trait, genotyping of SNPs (n = 27) in OC-related genes was performed. Candidate SNPs were chosen in genes with an emphasis on the vitamin D and vitamin K pathways. Multivariant factor analysis revealed a correlation between vitamin D serum concentration and a SNP in the gene GC (rs43338565), which encodes a vitamin D-binding protein, as well as between a SNP in NFATc1 (rs42038422) and OC concentration. However, univariate analysis revealed that population structure, vitamin D serum levels and SNPs were not significant determinants of OC status in the studied group.

Keywords

Osteocalcin;Vitamin D;Population Structure;Single Nucleotide Polymorphisms;D-loop;Bos taurus

References

  1. Arbour, N. C., H. M. Darwish and H. F. DeLuca. 1995. Transcriptional control of the osteocalcin gene by 1,25-dihydroxyvitamin D-2 and its 24-epimer in rat osteosarcoma cells. Biochim. Biophys. Acta 1263:147-153. https://doi.org/10.1016/0167-4781(95)00091-T
  2. Balding, D. J. 2006. A tutorial on statistical methods for population association studies. Nat. Rev. Genet. 7:781-791. https://doi.org/10.1038/nrg1916
  3. Breur, G. J., M. J. Allen, S. J. Carlson and D. C. Richardson. 2004. Markers of bone metabolism in dog breeds of different size. Res. Vet. Sci. 76:53-55. https://doi.org/10.1016/S0034-5288(03)00110-3
  4. Chen, C., X. Zhang and Y. Wang. 2010. Analysis of JAK2 and STAT3 polymorphisms in patients with ankylosing spondylitis in Chinese Han population. Clin. Immunol. (in press).
  5. Choo, M. K., H. Yeo and M. Zayzafoon. 2009. NFATc1 mediates HDAC-dependent transcriptional repression of osteocalcin expression during osteoblast differentiation. Bone 45:579-589. https://doi.org/10.1016/j.bone.2009.05.009
  6. Clement, M., D. Posada and K. A. Crandall. 2000. TCS: a computer program to estimate gene genealogies. Mol. Ecol. 9:1657-1659. https://doi.org/10.1046/j.1365-294x.2000.01020.x
  7. Desbois, C., D. A. Hogue and G. Karsenty. 1994. The mouse osteocalcin gene cluster contains three genes with two separate spatial and temporal patterns of expression. J. Biol. Chem. 269:1183-1190.
  8. Ducy, P., C. Desbois, B. Boyce, G. Pinero, B. Story, C. Dunstan, E. Smith, J. Bonadio, S. Goldstein and C. Gundberg. 1996. Increased bone formation in osteocalcin-deficient mice. Nature 382:448-452. https://doi.org/10.1038/382448a0
  9. Engelman, C. D., T. E. Fingerlin, C. D. Langefeld, P. J. Hicks, S. S. Rich, L. E. Wagenknecht, D. W. Bowden and J. M. Norris. 2008. Genetic and environmental determinants of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels in Hispanic and African Americans. J. Clin. Endocrinol. Metab. 93:3381-3388. https://doi.org/10.1210/jc.2007-2702
  10. Ewens, W. J. and R. S. Spielman. 1995. The transmission/disequilibrium test: history, subdivision, and admixture. Am. J. Hum. Genet. 57:455-464. https://doi.org/10.1002/ajmg.1320570319
  11. Ezura, Y., T. Nakajima, M. Kajita, R. Ishida, S. Inoue, H. Yoshida, T. Suzuki, M. Shiraki, T. Hosoi and H. Orimo. 2003. Association of molecular variants, haplotypes, and linkage disequilibrium within the human vitamin D-binding protein (DBP) gene with postmenopausal bone mineral density. J. Bone Miner. Res. 18:1642-1649. https://doi.org/10.1359/jbmr.2003.18.9.1642
  12. Ferland, G. 1998. The vitamin K-dependent proteins: an update. Nutr. Rev. 56:223-230.
  13. Garnero, P., F. Munoz, E. Sornay-Rendu and P. D. Delmas. 2007. Associations of vitamin D status with bone mineral density, bone turnover, bone loss and fracture risk in healthy postmenopausal women. The OFELY study. Bone. 40:716-722.
  14. Goring, H. H., J. D. Terwilliger and J. Blangero. 2001. Large upward bias in estimation of locus-specific effects from genomewide scans. Am. J. Hum. Genet. 69:1357-1369. https://doi.org/10.1086/324471
  15. Gundberg, C. M., A. C. Looker, S. D. Nieman and M. S. Calvo. 2002. Patterns of osteocalcin and bone specific alkaline phosphatase by age, gender, and race or ethnicity. Bone 31:703-708. https://doi.org/10.1016/S8756-3282(02)00902-X
  16. Huber, K. T., M. Langton, D. Penny, V. Moulton and M. Hendy. 2002. Spectronet: a package for computing spectra and median networks. Appl. Bioinformatics 1:159-161.
  17. Huelsenbeck, J. P. and B. Rannala. 1996. Combining data in phylogenetic analysis. Trends Ecol. Evol. 11:152-158. https://doi.org/10.1016/0169-5347(96)10006-9
  18. Jia, S., H. Chen, G. Zhang, Z. Wang, C. Lei, R. Yao and X. Han. 2007. Genetic variation of mitochondrial D-loop region and evolution analysis in some Chinese cattle breeds. J. Genet. Genomics 34:510-518. https://doi.org/10.1016/S1673-8527(07)60056-3
  19. Kinoshita, H., K. Nakagawa, K. Narusawa, M. Goseki-Sone, M. Fukushi-Irie, L. Mizoi, H. Yoshida, T. Okano, T. Nakamura and T. Suzuki. 2007. A functional single nucleotide polymorphism in the vitamin-K-dependent gamma-glutamyl carboxylase gene (Arg325Gln) is associated with bone mineral density in elderly Japanese women. Bone 40:451-456. https://doi.org/10.1016/j.bone.2006.08.007
  20. Kumar, S., M. Nei, J. Dudley and K. Tamura. 2008. MEGA: a biologist-centric software for evolutionary analysis of DNA and protein sequences. Brief. Bioinform 9:299-306. https://doi.org/10.1093/bib/bbn017
  21. Lai, S. J., Y. P. Liu, Y. X. Liu, X. W. Liand Y. G. Yao. 2006. Genetic diversity and origin of Chinese cattle revealed by mtDNA D-loop sequence variation. Mol. Phylogenet. Evol. 38:146-154. https://doi.org/10.1016/j.ympev.2005.06.013
  22. Larkin, M. A., G. Blackshields, N. P. Brown, R. Chenna, P. A. McGettigan, H. McWilliam, F. Valentin, I. M. Wallace, A. Wilm and R. Lopez. 2007. Clustal W and Clustal X version 2.0. Bioinformatics 23:2947-2948. https://doi.org/10.1093/bioinformatics/btm404
  23. Lauridsen, A. L., P. Vestergaard, A. P. Hermann, C. Brot, L. Heickendorff, L. Mosekilde and E. Nexo. 2005. Plasma concentrations of 25-hydroxy-vitamin D and 1,25-dihydroxyvitamin D are related to the phenotype of Gc (vitamin Dbinding protein): a cross-sectional study on 595 early postmenopausal women. Calcif. Tissue Int. 77:15-22. https://doi.org/10.1007/s00223-004-0227-5
  24. Lei, C. Z., H. Chen, H. C. Zhang, X. Cai, R. Y. Liu, L. Y. Luo, C. F. Wang, W. Zhang, Q. L. Ge and R. F. Zhang. 2006. Origin and phylogeographical structure of Chinese cattle. Anim. Genet. 37:579-582. https://doi.org/10.1111/j.1365-2052.2006.01524.x
  25. Lei, S., F. Deng, P. Xiao, K. Zhong, H. Deng, R. R. Recker and H. Deng. 2009. Bivariate whole-genome linkage scan for bone geometry and total body fat mass. J. Genet. Genomics 36:89-97. https://doi.org/10.1016/S1673-8527(08)60095-8
  26. Lepage, O. M., D. J. Hartmann, R. Eicher, B. Uebelhart, P. Tschudi and D. Uebelhart. 1998. Biochemical markers of bone metabolism in draught and warmblood horses. Vet. J. 156:169-175. https://doi.org/10.1016/S1090-0233(98)80120-2
  27. Librado, P. and J. Rozas. 2009. DnaSP v5: a software for comprehensive analysis of DNA polymorphism data. Bioinformatics 25:1451-1452. https://doi.org/10.1093/bioinformatics/btp187
  28. Martinez, P., I. Moreno, F. De Miguel, V. Vila, P. Esbrit and M. E. Martinez. 2001. Changes in osteocalcin response to 1,25-dihydroxyvitamin D(3) stimulation and basal vitamin D receptor expression in human osteoblastic cells according to donor age and skeletal origin. Bone 29:35-41. https://doi.org/10.1016/S8756-3282(01)00479-3
  29. McCullough, M. L., R. M. Bostick and T. L. Mayo. 2009. Vitamin D gene pathway polymorphisms and risk of colorectal, breast, and prostate cancer. Annu. Rev. Nutr. 29:111-132. https://doi.org/10.1146/annurev-nutr-080508-141248
  30. Moreno-Reyes, R., Y. A. Carpentier, M. Boelaert, K. El Moumni, G. Dufourny, C. Bazelmans, A. Leveque, C. Gervy and S. Goldman. 2009. Vitamin D deficiency and hyperparathyroidism in relation to ethnicity: a cross-sectional survey in healthy adults. Eur. J. Nutr. 48:31-37. https://doi.org/10.1007/s00394-008-0756-1
  31. Pani, M. A., K. Regulla, M. Segni, S. Hofmann, M. Hufner, A. M. Pasquino, K. H. Usadel and K. Badenhoop. 2002. A polymorphism within the vitamin D-binding protein gene is associated with Graves' disease but not with Hashimoto's thyroiditis. J. Clin. Endocrinol. Metab. 87:2564-2567. https://doi.org/10.1210/jc.87.6.2564
  32. Pritchard, J. K. and N. A. Rosenberg. 1999. Use of unlinked genetic markers to detect population stratification in association studies. Am. J. Hum. Genet. 65:220-228. https://doi.org/10.1086/302449
  33. Pritchard, J. K., M. Stephens and P. Donnelly. 2000. Inference of population structure using multilocus genotype data. Genetics 155:945-959.
  34. Rodriguez, S., T. R. Gaunt and I. N. Day. 2009. Hardy-Weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies. Am. J. Epidemiol. 169:505-514.
  35. Ronquist, F. and J. P. Huelsenbeck. 2003. MrBayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics 19:1572-1574. https://doi.org/10.1093/bioinformatics/btg180
  36. Sabsovich, I., J. D. Clark, G. Liao, G. Peltz, D. P. Lindsey, C. R. Jacobs, W. Yao, T. Z. Guo and W. S. Kingery. 2008. Bone microstructure and its associated genetic variability in 12 inbred mouse strains: microCT study and in silico genome scan. Bone 42:439-451. https://doi.org/10.1016/j.bone.2007.09.041
  37. Sankararaman, S., S. Sridhar, G. Kimmel and E. Halperin. 2008. Estimating local ancestry in admixed populations. Am. J. Hum. Genet. 82:290-303. https://doi.org/10.1016/j.ajhg.2007.09.022
  38. Sherry, S. T., M. H. Ward, M. Kholodov, J. Baker, L. Phan, E. M. Smigielski and K. Sirotkin. 2001. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 29:308-311. https://doi.org/10.1093/nar/29.1.308
  39. Singh, V. K., A. K. Mangalam, S. Dwivedi and S. Naik. 1998. Primer premier: program for design of degenerate primers from a protein sequence. Biotechniques 24:318-319.
  40. Srivastava, A. K., S. Bhattacharyya, X. Li, S. Mohan and D. J. Baylink. 2001. Circadian and longitudinal variation of serum C-telopeptide, osteocalcin, and skeletal alkaline phosphatase in C3H/HeJ mice. Bone 29:361-367. https://doi.org/10.1016/S8756-3282(01)00581-6
  41. Stafford, D. W. 2005. The vitamin K cycle. J. Thromb. Haemost. 3:1873-1878. https://doi.org/10.1111/j.1538-7836.2005.01419.x
  42. Szulc, P., E. Seeman and P. D. Delmas. 2000. Biochemical measurements of bone turnover in children and adolescents. Osteoporos Int. 11:281-294. https://doi.org/10.1007/s001980070116
  43. Tamura, K., J. Dudley, M. Nei and S. Kumar. 2007. MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol. Biol. Evol. 24:1596-1599. https://doi.org/10.1093/molbev/msm092
  44. Teichert, M., L. E. Visser, R. H. van Schaik, A. Hofman, A. G. Uitterlinden, P. A. De Smet, J. C. Witteman and B. H. Stricker. 2008. Vitamin K epoxide reductase complex subunit 1 (VKORC1) polymorphism and aortic calcification: the Rotterdam Study. Arterioscler. Thromb. Vasc. Biol. 28:771-776. https://doi.org/10.1161/ATVBAHA.107.159913
  45. Winslow, M. M., M. Pan, M. Starbuck, E. M. Gallo, L. Deng, G. Karsenty and G. R. Crabtree. 2006. Calcineurin/NFAT signaling in osteoblasts regulates bone mass. Dev. Cell 10:771-782. https://doi.org/10.1016/j.devcel.2006.04.006
  46. Zhang, R., P. Ducy and G. Karsenty. 1997. 1,25-dihydroxyvitamin D3 inhibits Osteocalcin expression in mouse through an indirect mechanism. J. Biol. Chem. 272:110-116. https://doi.org/10.1074/jbc.272.1.110