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This Article Accepted manuscript (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 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.

S Mencej-Bedrac, Department of Clinical Biochemistry, University of Ljubljana, Faculty of Phamacy, Ljubljana, Slovenia
J Prezelj, Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre, Ljubljana, Slovenia
T Kocjan, Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre, Ljubljana, Slovenia
K Teskac, Department of Phamaceutical Technology, University of Ljubljana, Faculty of Phamacy, Ljubljana, Slovenia
B Ostanek, Department of Clinical Biochemistry, University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia
M Smelcer, Department of Clinical Biochemistry, University of Ljubljana, Faculty of Phamacy, Ljubljana, Slovenia
J Marc, Department of Clinical Biochemistry, University of Ljubljana, Faculty of Phamacy, Ljubljana, Slovenia

Correspondence: Simona Mencej-Bedrac, Email: simona.mencej{at}ffa.uni-lj.si

Abstract

1,25-dihydroxyvitamin D3 upregulates tumour necrosis factor superfamily member 11 (TNFSF11), that codes for receptor activator of nuclear factor B ligand (RANKL), and downregulates osteoprotegerin (OPG) expression. In our study, we analyzed the individual effects and searched for combined interactions of polymorphisms in the vitamin D receptor (VDR), OPG and TNFSF11.

We evaluated 641 subjects: 239 osteoporotic and 228 non-osteoporotic postmenopausal, 57 premenopausal women and 117 elderly men. Subjects were genotyped for BsmI, FokI and Cdx2 in VDR, K3N in OPG and -290CT, -643CT and -693GC in TNFSF11 gene. Bone mineral density (BMD) and biochemical markers were measured.

In 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 290CT(TNFSF11) (p=0.021 and 0.017). No association with BMD was found in non-osteoporotic women. In premenopausal 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 290CT(TNFSF11)-K3N(OPG) combination was associated with BMD-th (p=0.041) in osteoporotic women. In 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 290CT(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 in larger cohorts.