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Associations of catalase gene polymorphisms with bone mineral density and bone turnover markers in postmenopausal women

¹ National Genome Research Institute, National Institute of Health, Seoul, Korea
² Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, Daegu, Korea
³ Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
⁴ Department of Genetic Epidemiology, SNP Genetics, Seoul, Korea

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] 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 +22348CT 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 +22348CT polymorphism and HT4 of CAT may be useful genetic markers for bone metabolism.

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

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