Gene-gene interactions in RANK/RANKL/OPG system influence bone mineral density in postmenopausal women
Zupan, Janja (Author), Mencej Bedrač, Simona (Author), Jurković Mlakar, Simona (Author), Preželj, Janez (Author), Marc, Janja (Author)

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Receptor activator of nuclear factor ?B (RANK) is one of the proteins in regulation of osteoclastogenesis via RANK/RANKL/OPG. Gene that codes for RANK protein (TNFRSF11A) was associated with osteoporotic fractures in a recent genome-wide association study. As variations in the RANK gene could alter its expression and activity, the aim of our study was to evaluate the influence offour RANK gene polymorphisms on bone mineral density (BMD) and biochemical markers. We evaluated 467 postmenopausal women and 117 elderly men. All subjects were genotyped for the presence of RANK polymorphisms -670G > C, +34694C > T, +34901G > A and +35966insdelC. BMD and biochemical markers were measured. Significant associations of +35966insdelC with BMD at lumbar spine (BMD-ls), total hip (BMD-th) and femoral neck (BMD-fn) were found in postmenopausal women (p = 0.020, 0.024 and 0.034), but not in men. Significantgene-gene interaction was proved for two RANK polymorphisms in combination with OPG and RANKL polymorphisms studied previously in postmenopausal women. Firstly, RANK/RANKL (+34901G > A/-290C>T) combination was associated with BMD-fn, BMD-th and BMD-ls (p = 0.034, 0.016 and 0.050), and secondly, RANK/OPG combination (+35966insdelC/K3N) showed influence on BMD-fn and BMD-ls (p = 0.043 and 0.039). Our results suggest that gene-gene interactions between RANK and OPG, and RANK and RANKL influence BMD in postmenopausal women.

Keywords:osteoporoza, postmenopavzna, SNP, RANKL
Work type:Not categorized (r6)
Tipology:1.01 - Original Scientific Article
Organization:FFA - Faculty of Pharmacy
Number of pages:str. 102-106
Numbering:Vol. 118, iss. 1-2
ISSN on article:0960-0760
COBISS.SI-ID:2701425 Link is opened in a new window
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Record is a part of a journal

Title:Journal of Steroid Biochemistry and Molecular Biology
Shortened title:J Steroid Biochem Mol Biol
Publisher:Pergamon Press
COBISS.SI-ID:527636 This link opens in a new window

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