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HSD11B1 polymorphisms predicted bone mineral density and fracture risk in postmenopausal women without a clinically apparent hypercortisolemia
Authors:Joo-Yeon Hwang  Seung Hun Lee  Ghi Su Kim  Jung-Min Koh  Min Jin Go  Young-Jin Kim  Hyung-Cheol Kim  Tae-Ho Kim  Jung Min Hong  Eui Kyun Park  Jong-Young Lee  Shin-Yoon Kim
Affiliation:1. Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea;2. Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Republic of Korea;3. Center for Antimicrobial Resistance and Microbial Genetics, University of Ulsan, Seoul, Republic of Korea;4. Division of Bacterial Respiratory Infections, National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongwon-gun, Republic of Korea;5. Project Team, Dongwha Pharm Co. Ltd, Seoul, Republic of Korea;6. Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;1. Department of Internal medicine, Yonsei University College of medicine, Seoul, Republic of Korea;2. Institute of Gastroenterology, Yonsei University College of medicine, Seoul, Republic of Korea;3. Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea;4. Department of Internal Medicine, Cha Bundang Medical Center, Cha University, Seongnam, Republic of Korea;5. Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China;6. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China;7. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong; Hong Kong SAR, China
Abstract:IntroductionEndogenous glucocorticoid (GC) may participate in bone physiology, even in subjects with no glucocorticoid excess. 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) is a primary regulator catalyzing the reduction of inactive cortisone to active cortisol. To elucidate genetic relevance of HSD11B1 variants to vertebral fracture and osteoporosis, we investigated the potential involvement of six HSD11B1 SNPs in postmenopausal women.MethodsAll exons, their boundaries and the promoter region (approximately 1.5 kb) were directly sequenced in 24 individuals. Six polymorphisms were selected and genotyped in all study participants (n = 1329). BMD was measured using dual-energy X-ray absorptiometry.ResultsHSD11B1 + 16374C>T and + 27447G>C were associated with reduced vertebral fracture risk (p = 0.016 and 0.032, respectively). Two of these (LD block2) in intron 5 (rs1000283 and rs932335) were significantly associated with bone mineral density (BMD) at the femoral neck (p = 0.00005 and 0.0002, respectively). Specifically, HSD11B1 + 16374C>T and + 27447G>C polymorphisms were associated with higher BMD values of the femoral neck in multiple comparison (p = 0.0002 and 0.0004, respectively) and Bonferroni corrected significance level (97% power). Consistent with these results, HSD11B1-ht21 and -ht22 comprising both SNPs also showed the evidence of association with BMD values of the femoral neck (pdomiant = 0.0002 and precessive = 0.00005, respectively).ConclusionOur results provide preliminary evidence supporting an association of HSD11B1 with osteoporosis in postmenopausal women. Also, these findings demonstrate that + 16374C>T polymorphism may be useful genetic markers for bone metabolism.
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