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, P. Lakatos, Miklós Tóth, K. Rácz, A. Patócs

Research output: Contribution to journalArticle

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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 2012

Fingerprint

Polymorphism
Genetic Promoter Regions
Bone Density
Minerals
Bone
Genes
Single Nucleotide Polymorphism
Luciferases
Assays
Metabolism
Association reactions
11-beta-Hydroxysteroid Dehydrogenases
Bone and Bones
Enzymes
Glucocorticoids
Alleles
HapMap Project
Postmenopausal Osteoporosis
Tissue
Femur Neck

Keywords

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

ASJC Scopus subject areas

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

Cite this

The rs4844880 polymorphism in the promoter region of the HSD11B1 gene associates with bone mineral density in healthy and postmenopausal osteoporotic women. / Feldman, Karolina; Szappanos, Ágnes; Butz, Henriett; Grolmusz, Vince; Majnik, Judit; Likó, István; Kriszt, Balázs; Lakatos, P.; Tóth, Miklós; Rácz, K.; Patócs, A.

In: Steroids, Vol. 77, No. 13, 11.2012, p. 1345-1351.

Research output: Contribution to journalArticle

Feldman, Karolina ; Szappanos, Ágnes ; Butz, Henriett ; Grolmusz, Vince ; Majnik, Judit ; Likó, István ; Kriszt, Balázs ; Lakatos, P. ; Tóth, Miklós ; Rácz, K. ; Patócs, A. / The rs4844880 polymorphism in the promoter region of the HSD11B1 gene associates with bone mineral density in healthy and postmenopausal osteoporotic women. In: Steroids. 2012 ; Vol. 77, No. 13. pp. 1345-1351.
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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.",
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T1 - The rs4844880 polymorphism in the promoter region of the HSD11B1 gene associates with bone mineral density in healthy and postmenopausal osteoporotic women

AU - Feldman, Karolina

AU - Szappanos, Ágnes

AU - Butz, Henriett

AU - Grolmusz, Vince

AU - Majnik, Judit

AU - Likó, István

AU - Kriszt, Balázs

AU - Lakatos, P.

AU - Tóth, Miklós

AU - Rácz, K.

AU - Patócs, A.

PY - 2012/11

Y1 - 2012/11

N2 - 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.

AB - 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.

KW - 11 β-hydroxysteroid dehydrogenase type 1

KW - Bone mineral density

KW - Osteoporosis

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