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

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 38kb 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.