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) 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 Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Mencej, S. Articles by Marc, J. Search for Related Content PubMed PubMed Citation Articles by Mencej, S. Articles by Marc, J.

Simona Mencej, Omar M E Albagha¹, Janez Preelj², Toma Kocjan²

Faculty of Pharmacy, Chair of Clinical Biochemistry, University of Ljubljana, Askerceva cesta 7, SI-1000 Ljubljana, Slovenia ¹ Rheumatology Section, Molecular Medicine Centre, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, UK ² Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre, Zaloska cesta 2, SI-1000 Ljubljana, Slovenia

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

Tumour necrosis factor superfamily member 11 (TNFSF11) gene, that codes for receptor activator of nuclear factor-B ligand, is one of the candidate genes for the genetic susceptibility to osteoporosis. As variations in the TNFSF11 gene promoter could alter its expression, the aim of the study was to evaluate the functional influence of three polymorphisms in the promoter and to investigate their association with bone mineral density (BMD) and biochemical markers in postmenopausal women. A total of 404 postmenopausal women were genotyped for the presence of TNFSF11 gene promoter polymorphisms –290C>T, –643C>T and –693G>C. Two common haplotypes, CCG and TTC, which occur in 44.3 and 49.3% of subjects respectively, were subjected to functional analysis. Amplified fragments were cloned into pGL3-basic reporter plasmid, which was co-transfected with pRL-TK plasmid into HEK293 cells. Dual luciferase reporter assay was performed. BMD and biochemical markers were measured. Reporter gene analysis showed significantly higher luciferase activity in CCG than in TTC haplotype (P=0.018). Both showed association with lumbar spine BMD (BMD-ls; P=0.005 and 0.007 for TTC and CCG respectively), whereas in femoral neck there was no association with BMD. In postmenopausal osteoporosis, association with BMD-ls was established in –290C>T, –643C>T and –693G>C (P values: 0.001, 0.041 and 0.013 respectively). Association with femoral neck BMD was shown in –693G>C (P=0.049). No association was found with biochemical markers in any of the groups. Our results suggest that in postmenopausal osteoporosis, TNFSF11 gene promoter polymorphisms –290C>T, –643C>T and –693G>C play a functional role in the genetic regulation of BMD.

This article has been cited by other articles:

				S. Mencej-Bedrac, J. Prezelj, T. Kocjan, K. Teskac, B. Ostanek, M. Smelcer, and J. Marc The combinations of polymorphisms in vitamin D receptor, osteoprotegerin and tumour necrosis factor superfamily member 11 genes are associated with bone mineral density J. Mol. Endocrinol., March 1, 2009; 42(3): 239 - 247. [Abstract] [Full Text] [PDF]