Journal of Genetic Medicine

Korean Society of Medical Genetics and Genomics (대한의학유전학회)
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Identification of novel susceptibility genes associated with bone density and osteoporosis in Korean women

  • Bo-Young Kim (Department of Medical Genetics, Ajou University School of Medicine) ;
  • Do-Wan Kim (Department of Medical Genetics, Ajou University School of Medicine) ;
  • Eunkuk Park (Department of Medical Genetics, Ajou University School of Medicine) ;
  • Jeonghyun Kim (Department of Medical Genetics, Ajou University School of Medicine) ;
  • Chang-Gun Lee (Department of Medical Genetics, Ajou University School of Medicine) ;
  • Hyun-Seok Jin (Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University) ;
  • Seon-Yong Jeong (Department of Medical Genetics, Ajou University School of Medicine)
  • Received : 2022.11.13
  • Accepted : 2022.12.16
  • Published : 2022.12.31
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Abstract

Purpose: Osteoporosis is a common calcium and metabolic skeletal disease which is characterized by decreased bone mass, microarchitectural deterioration of bone tissue and impaired bone strength, thereby leading to enhanced risk of bone fragility. In this study, we aimed to identify novel genes for susceptibility to osteoporosis and/or bone density. Materials and Methods: To identify differentially expressed genes (DEGs) between control and osteoporosis-induced cells, annealing control primer-based differential display reverse-transcription polymerase chain reaction (RT-PCR) was carried out in pre-osteoblast MC3T3-E1 cells. Expression levels of the identified DEGs were evaluated by quantitative RT-PCR. Association studies for the quantitative bone density analysis and osteoporosis case-control analysis of single nucleotide polymorphism (SNPs) were performed in Korean women (3,570 subjects) from the Korean Association REsource (KARE) study cohort. Results: Comparison analysis of expression levels of the identified DEGs by quantitative RT-PCR found seven genes, Anxa6, Col5a1, Col6a2, Eno1, Myof, Nfib, and Scara5, that showed significantly different expression between the dexamethason-treated and untreated MC3T3-E1 cells and between the ovariectomized osteoporosis-induced mice and sham mice. Association studies revealed that there was a significant association between the SNPs in the five genes, ANXA6, COL5A1, ENO1, MYOF, and SCARA5, and bone density and/or osteoporosis. Conclusion: Using a whole-genome comparative expression analysis, gene expression evaluation analysis, and association analysis, we found five genes that were significantly associated with bone density and/or osteoporosis. Notably, the association P-values of the SNPs in the ANXA6 and COL5A1 genes were below the Bonferroni-corrected significance level.

Keywords

Acknowledgement

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institution (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant no. HR22C1734), the Korea Initiative for fostering University of Research and Innovation Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. NRF2021M3H1A104892211), and an intramural research grant from the Korea National Institute of Health (2020-NG-021).

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