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Associations of catalase gene polymorphisms with bone mineral density and bone turnover markers in postmenopausal women
  1. Bermseok Oh1,*,
  2. Shin-Yoon Kim2,*,
  3. Duk Jae Kim3,
  4. Jong Yong Lee1,
  5. Jong-Keuk Lee1,
  6. Kuchan Kimm1,
  7. Byung Lae Park4,
  8. Hyoung Doo Shin4,
  9. Tae-Ho Kim2,
  10. Eui Kyun Park2,
  11. Jung-Min Koh3,
  12. Ghi Su Kim3
  1. 1National Genome Research Institute, National Institute of Health, Seoul, Korea
  2. 2Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, Daegu, Korea
  3. 3Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  4. 4Department of Genetic Epidemiology, SNP Genetics, Seoul, Korea
  1. Correspondence to:
 G S Kim
 Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea; gskim3{at}amc.seoul.kr

Abstract

Background: Oxidative stress has been recently suggested to play a part in the development of osteoporosis. Catalase is a major antioxidant enzyme that detoxifies hydrogen peroxide by converting it into water and oxygen, thereby preventing cellular injury by oxidative stress.

Aims: To examine the associations between the catalase gene (CAT) polymorphisms and bone mineral density (BMD) and bone turnover markers in postmenopausal Korean women.

Methods: All exons, their boundaries and the promoter region (approximately 1.5 kb) were directly sequenced in 24 individuals. Among 18 variants identified by a direct sequence method, four polymorphisms were selected and genotyped in all study participants (n = 560). BMD at the lumbar spine and proximal femur was measured using dual-energy x ray absorptiometry. Serum osteocalcin concentrations and bone-specific alkaline phosphatase activity were determined by an immunoradiometric assay and an immunoassay, respectively.

Results: The mean (standard deviation) age of the participants was 59.4 (7.2) years. Multivariate analysis showed an association of the +22348C→T polymorphism with BMD at the lumbar spine (p = 0.01 in the dominant model) and at femur neck (p = 0.05 in the dominant model), and with serum osteocalcin level (p = 0.008 in the dominant model). Haplotype analyses showed that HT4 (−20T, +144C, +22348T, +33078A) was significantly associated with higher BMD at various sites (p<0.001–0.03) and with lower serum osteocalcin levels (p = 0.01 in the codominant model).

Conclusions: These findings indicate that the +22348C→T polymorphism and HT4 of CAT may be useful genetic markers for bone metabolism.

  • BMD, bone mineral density
  • CAT, catalase gene
  • ROS, reactive oxygen species
  • SNP, single-nucleotide polymorphism
  • YSM, years since menopause

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Footnotes

  • * These authors contributed equally to this work.

  • Funding: This work was supported by a grant from the Korea Health 21 R & D Project, Ministry of Health and Welfare, Republic of Korea (Project 01-PJ3-PG6-01GN111-0002).

  • Competing interests: None.

  • Ethical approval: This study was approved by the institutional review board of the Asan Medical Center, and written informed consent was obtained from each participant.