HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: JME-08-0108v1 42/3/239    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mencej-Bedrac, S. Articles by Marc, J. Search for Related Content PubMed PubMed Citation Articles by Mencej-Bedrac, S. Articles by Marc, J.

Simona Mencej-Bedra, Janez Preelj¹, Toma Kocjan¹, Karmen Teska², Barbara Ostanek, Mojca melcer

Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Askerceva cesta 7, SI-1000 Ljubljana, Slovenia¹ Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre, Zaloska cesta 2, SI-1000 Ljubljana, Slovenia² Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ljubljana, Askerceva cesta 7, SI-1000 Ljubljana, Slovenia

(Correspondence should be addressed to J Marc; Email: janja.marc{at}ffa.uni-lj.si)

1,25-dihydroxyvitamin D₃ upregulates tumour necrosis factor superfamily member 11 (TNFSF11) that codes for the receptor activator of nuclear factor B ligand (RANKL), and downregulates osteoprotegerin (OPG) expression. We have analyzed the individual effects of polymorphisms in the vitamin D receptor gene (VDR), OPG and TNFSF11, and searched for interactions between them. Six hundred and forty one subjects were evaluated: 239 osteoporotic and 228 non-osteoporotic post-menopausal, 57 pre-menopausal women and 117 elderly men. The subjects were genotyped for BsmI, FokI and Cdx2 in VDR, K3N in OPG and –290C>T, –643C>T and –693G>C in TNFSF11 gene. Bone mineral density (BMD) and biochemical markers were measured. In the osteoporotic women, femoral neck BMD (BMD-fn) showed associations with BsmI(VDR) and Cdx2(VDR) (P=0.015 and 0.047 respectively), and lumbar spine BMD (BMD-ls) with K3N(OPG) and –290C>T(TNFSF11) (P=0.021 and 0.017). No association with BMD was found in the non-osteoporotic women. In the pre-menopausal women, the Cdx2(VDR) polymorphism was associated with BMD-fn and total hip BMD (P=0.011 and 0.011). In elderly men, FokI(VDR) was associated with BMD-fn and BMD-ls (P=0.040 and 0.036). Interestingly, the –290C>T(TNFSF11)-K3N(OPG) combination was associated with BMD-th (P=0.041) in the osteoporotic women. In the non-osteoporotic women, the combination K3N(OPG)-Cdx2(VDR) was associated with BMD-ls, BMD-th and BMD-fn (P=0.032, 0.049 and 0.022), and the combination –290C>T(TNFSF11)-K3N(OPG) with BMD-fn (P=0.029). For the first time, the presence of gene–gene interactions between VDR, OPG and TNFSF11 genes was studied. Our results strongly suggest further confirmation of their combined influence on larger cohorts.

This article has been cited by other articles:

				K. A. Bishop, M. B. Meyer, and J. W. Pike A Novel Distal Enhancer Mediates Cytokine Induction of Mouse Rankl Gene Expression Mol. Endocrinol., December 1, 2009; 23(12): 2095 - 2110. [Abstract] [Full Text] [PDF]