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Cited by 55Bone health and osteoporosis researchGenetic Associations and EpidemiologyHormonal Regulation and Hypertension

HSD11B1 polymorphisms predicted bone mineral density and fracture risk in postmenopausal women without a clinically apparent hypercortisolemia

Hwang, Joo-Yeon, Lee, Seung Hun, Kim, Ghi Su, Koh, Jung-Min, Go, Min Jin, Kim, Young-Jin, Kim, Hyung-Cheol, Kim, Tae-Ho +4 more·2009·Bone
DOI 10.1016/j.bone.2009.07.080
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Abstract

Introduction Endogenous glucocorticoid (GC) may participate in bone physiology, even in subjects with no glucocorticoid excess. 11beta-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.Methods All 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.Results HSD11B1 +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 (p(domiant)=0.0002 and p(recessive)=0.00005, respectively).Conclusion Our 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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  • Glucocorticoid sensitivity may differ among individuals and among tissues within the same individual, partly because of polymorphisms in the glucocorticoid receptor and 11β-hydroxysteroid dehydrogenase type 1 genes.

    “the glucocorticoid sensitivity may be different among the different individuals and among the different tissues in the same individual, due also to polymorphisms of both glucocorticoid receptor (25)(26)(27)(28) and 11␤-hydroxysteroid-dehydrogenase type 1 genes (29,30).”

    From Diagnosis and Treatment of Subclinical Hypercortisolism (2011) · cites this paper as [30]

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Authors
Hwang, J.-Y., Lee, S. H., Kim, G. S., Koh, J.-M., Go, M. J., Kim, Y.-J., Kim, H.-C., Kim, T.-H., Hong, J. M., Park, E. K., Lee, J.-Y., & Kim, S.-Y.
Affiliations
  • Kyungpook National University Hospital (KR)
  • Korea National Institute of Health (KR)
  • Kyungpook National University (KR)
Corresponding author
  • Lee, Seung Hun
  • Kim, Ghi Su
  • Kim, Young-Jin
  • Kim, Hyung-Cheol
  • Lee, Jong-Young
  • Kim, Shin-Yoon
ORCID
Venue
Bone
Publisher
Elsevier BV
Published
2009-12
Volume
45
Issue
6
Pages
1098-1103
ISSN
  • 1873-2763 (ISSN-L)
  • 8756-3282
DOI
10.1016/j.bone.2009.07.080
OpenAlex
W2018322751
Cited by
55
References
40
Citations by year
2025: 4 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 4 · 2014: 2 · 2013: 9 · 2012: 3
FWCI
3.85
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Bone (publishedVersion)
  • PubMed (publishedVersion)
Funders
Centers for Disease Control and Prevention
Topics
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
Keywords
11β-hydroxysteroid dehydrogenase type 1, single nucleotide polymorphisms, bone mineral density, vertebral fractures, osteoporosis, postmenopausal women, endogenous glucocorticoids, genetic association, femoral neck, genetic markers
MeSH terms
Cushing Syndrome, Female, Femur Neck, Haplotypes, Humans, Middle Aged, Regression Analysis, Risk Factors, Bone Density, Linkage Disequilibrium, Spinal Fractures, Postmenopause, Polymorphism, Single Nucleotide, 11-beta-Hydroxysteroid Dehydrogenase Type 1, Fractures, Bone

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