Skip to main content

Advertisement

Log in

Association of osteoporosis with genetic variants of circadian genes in Chinese geriatrics

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

Abstract

Summary

This study was designed to investigate the association of circadian gene single nucleotide polymorphisms (SNPs) with the risk of osteoporosis. We found that the rs3781638 GG genotype was positively associated with osteoporosis prevalence in females, whereas the rs2292910 AC genotype was negatively associated with osteoporosis prevalence in a geriatric cohort.

Introduction

Studies have shown that disruption of endogenous circadian rhythms may increase the risk of developing type II diabetes and obesity, which are reportedly associated with osteoporosis (OP). Thus, abnormalities of circadian genes may indirectly induce OP. Here, we investigated the association of OP with 14 SNPs located in seven circadian genes.

Methods

The research subjects, geriatric residents of Shanghai Minhang, China, diagnosed with OP (N = 171) or osteopenia (N = 226) or without specific diseases (N = 200), were genotyped for 14 genetic variants of circadian genes by competitive allele-specific polymerase chain reaction. The prevalence of polymorphisms among the subject groups and the association between the SNPs and osteoporosis were investigated.

Results

Among the 14 genotyped SNPs, we found an association between the CRY2 gene rs2292910 SNP and osteoporosis (r = −0.082, p = 0.045) in the geriatric cohort. We found a decreased risk between cryptochrome 2 rs2292910 and OP (A/C odds ratio = 0.647, p = 0.044) but an increased risk between MTNR1B rs3781638 and OP (G/G odds ratio = 2.058, p = 0.044).

Conclusion

For the first time, we show that Cry 2 rs2292910 and MTNR1B rs3781638 are associated with osteoporosis in a Chinese geriatric cohort. Therefore, targeting the abnormalities of the CRY2 and MTNR1B genes may be a potential strategy to treat and/or to prevent osteoporosis.

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

Access this article

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. Harvey NC, Matthews P, Collins R, Cooper C (2013) Osteoporosis epidemiology in UK Biobank: a unique opportunity for international researchers. Osteoporos Int 24:2903–2905

    Article  CAS  PubMed  Google Scholar 

  2. Clark GR, Duncan EL (2015) The genetics of osteoporosis. Br Med Bull 113:73–81

    Article  CAS  PubMed  Google Scholar 

  3. Wu FY, Liu CS, Liao LN et al (2014) Vitamin D receptor variability and physical activity are jointly associated with low handgrip strength and osteoporosis in community-dwelling elderly people in Taiwan: the Taichung Community Health Study for Elders (TCHS-E). Osteoporos Int 25:1917–1929

    Article  CAS  PubMed  Google Scholar 

  4. Luo L, Xia W, Nie M, Sun Y, Jiang Y, Zhao J, He S, Xu L (2014) Association of ESR1 and C6orf97 gene polymorphism with osteoporosis in postmenopausal women. Mol Biol Rep 41:3235–3243

    Article  CAS  PubMed  Google Scholar 

  5. Tural S, Alayli G, Kara N, Tander B, Bilgici A, Kuru O (2013) Association between osteoporosis and polymorphisms of the IL-10 and TGF-beta genes in Turkish postmenopausal women. Hum Immunol 74:1179–1183

    Article  CAS  PubMed  Google Scholar 

  6. Tural S, Kara N, Alayli G, Tomak L (2013) Association between osteoporosis and polymorphisms of the bone Gla protein, estrogen receptor 1, collagen 1-A1 and calcitonin receptor genes in Turkish postmenopausal women. Gene 515:167–172

    Article  CAS  PubMed  Google Scholar 

  7. Vieira E, Ruano EG, Figueroa ALC, Aranda G, Momblan D, Carmona F, Gomis R, Vidal J, Hanzu FA (2014) Altered clock gene expression in obese visceral adipose tissue is associated with metabolic syndrome. PLoS ONE 9(11), e111678

    Article  PubMed  PubMed Central  Google Scholar 

  8. Medeiros R, Kelly MA, Rees SD et al (2012) Circadian gene variants and susceptibility to type 2 diabetes: a pilot study. PLoS ONE 7, e32670

    Article  Google Scholar 

  9. Hoffman AE, Zheng T, Yi CH, Stevens RG, Ba Y, Zhang Y, Leaderer D, Holford T, Hansen J, Zhu Y (2010) The core circadian gene cryptochrome 2 influences breast cancer risk, possibly by mediating hormone signaling. Cancer Prev Res 3:539–548

    Article  CAS  Google Scholar 

  10. Katsuya T, Sugimoto K, Hozawa A, Ohkubo T, Ohkubo T, Yamamoto K, Matsuo A, Ogihara T (2003) Genetic risk factors for cerebral infarction using data from a large scale genetic epidemiological study: the Ohasama study. Geriatr Gerontol Int 3(3):150–153

    Article  Google Scholar 

  11. Marques FZ, Campain AE, Davern PJ, Yang YH, Head GA, Morris BJ (2011) Genes influencing circadian differences in blood pressure in hypertensive mice. PLoS ONE 6(4), e19203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Maronde E, Schilling AF, Seitz S, Schinke T, Schmutz I, van der Horst G, Amling M, Albrecht U (2010) The clock genes period 2 and cryptochrome 2 differentially balance bone formation. PLoS ONE 5:e11527–e11535

    Article  PubMed  PubMed Central  Google Scholar 

  13. Lin F, Chen X, Li X, Zhao Q, Tan Z (2013) Over-expression of circadian clock gene Bmal1 affects proliferation and the canonical Wnt pathway in NIH-3T3 cells. Cell Biochem Funct 31(2):166–172

    Article  CAS  PubMed  Google Scholar 

  14. Kim H, Koh SY, Ku SH, Kim JH, Kim JG (2014) Association between polymorphisms in period genes and bone density in postmenopausal Korean women. Climacteric 17:605–612

    Article  CAS  PubMed  Google Scholar 

  15. Takarada T, Kodama A, Hotta S, Mieda M, Shimba S, Hinoi E, Yoneda Y (2012) Clock genes influence gene expression in growth plate and endochondral ossification in mice. J Biol Chem 287:36081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. He Y, Lin F, Chen Y, Tan Z, Bai D, Zhao Q (2015) Overexpression of the circadian clock GeneRev-erbαAffects murine bone mesenchymal stem cell proliferation and osteogenesis. Stem Cells Dev 24:1194–1204

    Article  CAS  PubMed  Google Scholar 

  17. Loboda A, Kraft WK, Fine B et al (2009) Diurnal variation of the human adipose transcriptome and the link to metabolic disease. BMC Med Genet 2:7

    Google Scholar 

  18. Sherman H, Genzer Y, Cohen R, Chapnik N, Madar Z, Froy O (2012) Timed high-fat diet resets circadian metabolism and prevents obesity. FASEB J 26(8):3493–3502

    Article  CAS  PubMed  Google Scholar 

  19. Zheng C, Dalla Man C, Cobelli C, Groop L, Zhao H, Bale AE, Shaw M, Duran E, Pierpont B, Caprio S, Santoro N (2015) A common variant in the MTNR1B gene is associated with increased risk of impaired fasting glucose (IFG) in youth with obesity. Obesity 23(5):1022–1029

    Article  PubMed  PubMed Central  Google Scholar 

  20. Been LF, Hatfield JL, Shankar A, Aston CE, Ralhan S, Wander GS, Mehra NK, Singh JR, Mulvihill JJ, Sanghera DK (2012) A low frequency variant within the GWAS locus of MTNR1B affects fasting glucose concentrations: genetic risk is modulated by obesity. Nutr Metab Cardiovasc Dis 22:944–951

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The study was supported by the Biobank of the Fifth People’s Hospital of Shanghai, Fudan University, by a research grant from the Shanghai Fifth Hospital of Fudan University (2014WYYJ10), by the Scientific Research Project of Shanghai Municipal Health and Family Planning Commission (201540203), and by Grants from the Zhejiang Province Natural Science Foundation (Y 14C200042).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to G. Yang or Y. Hong.

Ethics declarations

Conflicts of interest

None.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplemental Table 1

(DOCX 17 kb)

Supplemental Table 2

(DOCX 19 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Y., Zhou, J., Wu, Y. et al. Association of osteoporosis with genetic variants of circadian genes in Chinese geriatrics. Osteoporos Int 27, 1485–1492 (2016). https://doi.org/10.1007/s00198-015-3391-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-015-3391-8

Keywords

Navigation