The rs4844880 polymorphism in the promoter region of the HSD11B1 gene associates with bone mineral density in healthy and postmenopausal osteoporotic women

Karolina Feldman, Ágnes Szappanos, Henriett Butz, Vince Grolmusz, Judit Majnik, István Likó, Balázs Kriszt, Péter Lakatos, Miklós Tóth, Károly Rácz, Attila Patócs

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Introduction: The 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1) plays an important role in the regulation of local glucocorticoid concentration in a tissue specific manner. Previous studies indicated associations between polymorphisms (SNPs) of the HSD11B1 gene and laboratory as well as osteodensitometric parameters of bone metabolism. In our present work we examined whether the tagging HSD11B1 gene polymorphisms could influence bone metabolism in healthy and postmenopausal osteoporotic women. Experimental: HapMap database was used for identification and selection of SNPs located in the 38 kb range of the HSD11B1 gene. Twelve SNPs were selected and genotyped in 209 healthy control women using Taqman SNP assays on Real-Time PCR and direct DNA sequencing. Of these SNPs, the rs4844880 was genotyped in 154 women with postmenopausal osteoporosis. Functional characterization of the rs4844880 was performed by in vitro luciferase assay. Results: One of the 12 HSD11B1 SNPs, the rs4844880 showed a significant association with higher bone mineral density and/or T- and Z-scores at lumbar spine in healthy women. When data from 154 postmenopausal osteoporotic women were compared to those obtained from 101 age-matched postmenopausal healthy women selected from our healthy control group this association was strongly significant at the femoral neck region. In vitro luciferase assay demonstrated that the polymorphic rs4844880 allele inhibited the luciferase activity more significantly than the major allele. Conclusions: The rs4844880 polymorphism in the promoter region of the HSD11B1 gene resulting in a reduced expression of the enzyme may exert a beneficial effect on bone in healthy and postmenopausal osteoporotic women.

Original languageEnglish
Pages (from-to)1345-1351
Number of pages7
JournalSteroids
Volume77
Issue number13
DOIs
Publication statusPublished - Nov 1 2012

Keywords

  • 11 β-hydroxysteroid dehydrogenase type 1
  • Bone mineral density
  • Osteoporosis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

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