Skip to main content

Advertisement

SpringerLink
Log in

Polymorphisms of the WNT16 gene are associated with the heel ultrasound parameter in young adults

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

Bone mineral content is influenced by genetic factors. We investigated the role of WNT16 in bone properties determined using quantitative ultrasound (QUS) on young adults. Three WNT16 genetic markers (rs2908007, rs2908004, and rs2707466) were found to have a significant association with the broadband ultrasound attenuation (BUA) measurement, suggesting that WNT16 influences bone mass in young adults.

Introduction

The aim of this study was to investigate whether genetic markers on the WNT16 gene are associated with bone mass, as assessed using QUS in a population of healthy young Spanish adults.

Methods

A cross-sectional study was conducted on 575 individuals (mean age 20.41 ± 2.69). Bone quality was assessed using BUA measurements (dB/MHz) on the right calcaneus. Six single nucleotide polymorphisms (SNPs) (rs2908007, rs2908004, rs3801387, rs3801385, rs2707466, and rs2536184) covering the WNT16 gene were selected as genetic markers and genotyped to test their association with BUA variations.

Results

The rs2908007, rs2908004, and rs2707466 SNPs were found to have a significant association with BUA (p = 0.004, p = 0.001, and p = 0.004, respectively).

Conclusion

We demonstrate for the first time that WNT16 genetic polymorphisms influence QUS traits in a population of young adults. This finding suggests that WNT16 might be an important genetic factor in determining peak bone mass acquisition.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Genant HK, Cooper C, Poor G et al (1999) Interim report and recommendations of the World Health Organization Task-Force for Osteoporosis. Osteoporos Int 10(4):259–264

    Article  CAS  PubMed  Google Scholar 

  2. Arden NK, Baker J, Hogg C, Baan K, Spector TD (1996) The heritability of bone mineral density, ultrasound of the calcaneus and hip axis length: a study of postmenopausal twins. J Bone Miner Res 11:530–534

    Article  CAS  PubMed  Google Scholar 

  3. Howard GM, Nguyen TV, Harris M, Kelly PJ, Eisman JA (1998) Genetic and environmental contributions to the association between quantitative ultrasound and bone mineral density measurements: a twin study. J Bone Miner Res 13:1318–1327

    Article  CAS  PubMed  Google Scholar 

  4. Karasik D, Myers RH, Hannan MT, Gagnon D, McLean RR, Cupples LA, Kiel DP (2002) Mapping of quantitative ultrasound of the calcaneus bone to chromosome 1 by genome-wide linkage analysis. Osteoporos Int 13:796–802

    Article  CAS  PubMed  Google Scholar 

  5. Gueguen R, Jouanny P, Guillemin F, Kuntz C, Pourel J, Siest G (1995) Segregation analysis and variance components analysis of bone mineral density in healthy families. J Bone Miner Res 10:2017–2022

    Article  CAS  PubMed  Google Scholar 

  6. Pocock NA, Eisman JA, Hopper JL, Yeates MG, Sambrook PN, Eberl S (1987) Genetic determinantsof bone mass in adults. A twin study. J Clin Invest 80:706–710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Medina-Gomez C, Kemp JP, Estrada K et al (2012) Meta-analysis of genome-wide scans for total body BMD in children and adults reveals allelic heterogeneity and age-specific effects at the WNT16 locus. PLoS Genet 8(7), e1002718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Chesi A, Mitchell JA, Kalkwarf HJ, Bradfield JP, Lappe JM, McCormack SE, Gilsanz V, Oberfield SE, Hakonarson H, Shepherd JA, Kelly A, Zemel BS, Grant SFA (2015) A trans-ethnic genome-wide association study identifies gender specific loci influencing pediatric aBMD and BMC at the distal radius. Hum Mol Genet 3

  9. Moayyeri A, Hsu YH, Karasik D et al (2014) Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium. Hum Mol Genet 23:3054–3068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Garcia-Ibarbia C, Perez-Nunez MI, Olmos JM et al (2013) Missense polymorphisms of the WNT16 gene are associated with bone mass, hip geometry and fractures. Osteoporos Int 24(9):2449–2454

    Article  CAS  PubMed  Google Scholar 

  11. Zheng HF, Tobias JH, Duncan E et al (2012) WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk. PLoS Genet 8, e1002745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Estrada K, Styrkarsdottir U, Evangelou E, Hsu YH et al (2012) Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet 44:491–501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zhang L, Choi HJ, Estrada K et al (2014) Multistage genome-wide association meta-analyses identified two new loci for bone mineral density. Hum Mol Genet 23:1923–1933

    Article  CAS  PubMed  Google Scholar 

  14. Koller DL, Zheng HF, Karasik D et al (2012) Meta-analysis of genome-wide studies identifies WNT16 and ESR1 SNPS associated with bone mineral density in premenopausal women. J Bone Miner Res 28(3):547–558

    Article  Google Scholar 

  15. Hendrickx G, Boudin E, Fijalkowski I, Nielsen TL, Andersen M, Brixen K, Van Hul W (2014) Variation in the Kozak sequence of WNT16 results in an increased translation and is associated with osteoporosis related parameters. Bone 59:57–65

    Article  CAS  PubMed  Google Scholar 

  16. Logan CY, Nusse R (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20:781–810

    Article  CAS  PubMed  Google Scholar 

  17. Kobayashi Y, Uehara S, Koide M, Takahashi N (2015) The regulation of osteoclast differentiation by Wnt signals. Bone key Rep 4:713

    Google Scholar 

  18. Holroyd C, Harvey N, Dennison E, Cooper C (2012) Epigenetic influences in the developmental origins of osteoporosis. Osteoporos Int 23:401–410

    Article  CAS  PubMed  Google Scholar 

  19. Gluer CC, Eastell R, Reid DM et al (2004) Association of five quantitative ultrasound devices and bone densitometry with osteoporotic vertebral fractures in a population-based sample: the OPUS Study. J Bone Miner Res 19:782–793

    Article  PubMed  Google Scholar 

  20. Krieg MA, Barkmann R, Gonnelli S et al (2008) Quantitative ultrasound in the management of osteoporosis: the 2007 ISCD Official Positions. J Clin Densitom 11:163–187

    Article  PubMed  Google Scholar 

  21. Scheffler C, Gniosdorz B, Staub K, Rühli F (2014) Skeletal robustness and bone strength as measured by anthropometry and ultrasonography as a function of physical activity in young adults. Am J Hum Biol 26:215–220

    Article  PubMed  Google Scholar 

  22. Gombos Császár G, Bajsz V, Sió E, Steinhausz Tóth V, Schmidt B, Szekeres L, Kránicz J (2014) The direct effect of specific training and walking on bone metabolic markers in young adults with peak bone mass. Acta Physiol Hung 101:205–215

    Article  PubMed  Google Scholar 

  23. Timpson NJ, Tobias JH, Richards JB et al (2009) Common variants in the region around Osterixare associated with bone mineral density and growth in childhood. Hum Mol Genet 18:1510–1517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Craig CL, Marshall AL, Sjostrom M et al (2003) International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 35:1381–1395

    Article  PubMed  Google Scholar 

  25. Toyras J, Nieminen MT, Kroger H, Jurvelin JS (2002) Bone mineral density, ultrasound velocity, and broadband attenuation predict mechanical properties of trabecular bone differently. Bone 31:503–507

    Article  CAS  PubMed  Google Scholar 

  26. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265

    Article  CAS  PubMed  Google Scholar 

  27. Babaroutsi E, Magkos F, Manios Y, Sidossis LS (2005) Lifestyle factors affecting heel ultrasound in Greek females across different life stages. Osteoporos Int 16:552–561

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by grants CEI-2013-MP-4 and CEI-2014-MPBS28 from the Campus of International Excellence CEIBioTic Granada. M. Correa-Rodríguez was supported by an FPU Grant (Ministry of Education, Spanish Government). We would like to thank the staff of the Genomics and Genotyping Unit of GENyO (Granada) for their technical support.

Author information

Authors and Affiliations

  1. Department of Nursing, Faculty of Health Sciences, University of Granada (Spain), Av. Ilustración S/N, 18007, Granada, Spain

    M. Correa-Rodríguez, J. Schmidt Rio-Valle & B. Rueda-Medina

Authors
  1. M. Correa-Rodríguez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Schmidt Rio-Valle
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Rueda-Medina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Correa-Rodríguez.

Ethics declarations

All the procedures performed in the study involving human participants were undertaken in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflicts of interest

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Correa-Rodríguez, M., Schmidt Rio-Valle, J. & Rueda-Medina, B. Polymorphisms of the WNT16 gene are associated with the heel ultrasound parameter in young adults. Osteoporos Int 27, 1057–1061 (2016). https://doi.org/10.1007/s00198-015-3379-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-015-3379-4

Keywords

Search

Navigation