Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

IMPACT FACTOR 2017: 3.556

CiteScore 2017: 2.34

SCImago Journal Rank (SJR) 2017: 1.114
Source Normalized Impact per Paper (SNIP) 2017: 1.188

See all formats and pricing
More options …
Volume 44, Issue 9


Low-density lipoprotein receptor-related protein 5 and vitamin D receptor gene polymorphisms in relation to vitamin D levels in menopause

Katerina Zajickova / Martin Hill / Marketa Vankova / Ivana Zofkova
Published Online: 2011-09-21 | DOI: https://doi.org/10.1515/CCLM.2006.204


Background: The low-density lipoprotein receptor-related protein 5 (LRP5) gene has been recently identified as a novel candidate for osteoporosis. The c.4037C>T polymorphism in the LRP5 gene has been associated with bone mass variance in general population. In contrast, the IVS8+443G>A polymorphism in the vitamin D receptor gene (VDR) has not been investigated in relation to bone metabolism. The aim of the present study was to determine VDR IVS8+443G>A and LRP5 c.4037C>T polymorphisms in a cohort of 165 perimenopausal women and to associate the genotypes with biochemical and densitometric bone parameters in a subset of 112 postmenopausal women.

Methods: Both polymorphisms were assessed by restriction analysis of the PCR product. Calcium, parathyroid hormone, vitamin D metabolites and bone mineral density (BMD, g/cm2) at the hip and in the spine (L1–L4) were examined.

Results: The genotype frequencies of both IVS8+443G>A (UU 75.2%, Uu 23%, uu 1.8%) and c.4037C>T (CC 73.9% TC 23.6%, TT 2.4%) were comparable to other Caucasian female cohorts. Serum 25OH vitamin D levels, assessed in only 63 probands, were significantly associated with VDR genotypes (ANCOVA, p≤0.0027). We did not find any associations between LRP5 genotypes and bone or hormonal characteristics.

Conclusions: VDR IVS8+443G>A polymorphism was significantly associated with circulating 25OH vitamin D in postmenopausal Caucasian women. The role of candidate gene polymorphisms in the vitamin D metabolic pathway requires further investigation.

Clin Chem Lab Med 2006;44:1066–9.

Keywords: 25OH vitamin D; low-density lipoprotein receptor-related protein 5 gene; postmenopausal bone; single nucleotide polymorphisms; vitamin D receptor gene


  • 1.

    Peacock M, Turner CH, Econs MJ, Foroud T. Genetics of osteoporosis. Endocr Rev 2002; 23:303–26.Web of ScienceCrossrefGoogle Scholar

  • 2.

    Liu YZ, Liu YJ, Recker RR, Deng HW. Molecular studies of identification of genes for osteoporosis: the 2002 update. J Endocrinol 2003; 177:147–96.CrossrefGoogle Scholar

  • 3.

    Zajickova K, Krepelova A, Zofkova I. A single nucleotide polymorphism under the reverse primer binding site may lead to BsmI mis-genotyping in the vitamin D receptor gene. J Bone Miner Res 2003; 18:1754–7.CrossrefGoogle Scholar

  • 4.

    Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, et al. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 2001; 107:513–23.CrossrefGoogle Scholar

  • 5.

    Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, et al. High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med 2002; 346:1513–21.Google Scholar

  • 6.

    Okubo M, Horinishi A, Kim DH, Yamamoto TT, Murase T. Seven novel sequence variants in the human low density lipoprotein receptor related protein 5 (LRP5) gene. Hum Mutat 2002; 19:186.CrossrefGoogle Scholar

  • 7.

    Mizuguchi T, Furuta I, Watanabe Y, Tsukamoto K, Tomita H, Tsujihata M, et al. LRP5, low-density-lipoprotein-receptor-related protein 5, is a determinant for bone mineral density. J Hum Genet 2004; 49:80–6.CrossrefGoogle Scholar

  • 8.

    Ferrari SL, Deutsch S, Choudhury U, Chevalley T, Bonjour JP, Dermitzakis ET, et el. Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with variation in vertebral bone mass, vertebral bone size, and stature in whites. Am J Hum Genet 2004; 74:866–75.CrossrefGoogle Scholar

  • 9.

    Koay MA, Woon PY, Zhang Y, Miles LJ, Duncan EL, Ralston SH, et al. Influence of LRP5 polymorphisms on normal variation in BMD. J Bone Miner Res 2004; 19:1619–27.Google Scholar

  • 10.

    van Meurs JB, Rivadeneira F, Jhamai M, Hugens W, Hofman A, van Leeuwen J, et al. Common genetic variation of the low-density lipoprotein receptor-related protein 5 and 6 genes determines fracture risk in elderly white men. J Bone Miner Res 2006; 21:141–50.Google Scholar

  • 11.

    Fretz JA, Zella LA, Kim S, Shevde NK, Pike JW. 1,25-dihydroxyvitamin D3 regulates the expression of LDL-related protein 5 via DNAA sequence elements located downstream of the start site transcription. Mol Endocrinol 2006; Epub ahead of print, doi:10.1210/me.2006-0102.CrossrefGoogle Scholar

  • 12.

    Gong YL, Xie DW, Deng ZL, Bostick RM, Miao XJ, Zhang JH, et al. Vitamin D receptor gene Tru9I polymorphism and risk for incidental sporadic colorectal adenomas. World J Gastroenterol 2005; 11:4794–9.CrossrefGoogle Scholar

  • 13.

    Cooper GS, Umbach DM. Are vitamin D receptor polymorphisms associated with bone mineral density? A meta-analysis. J Bone Miner Res 1996; 11:1841–9.CrossrefGoogle Scholar

  • 14.

    Zee RY, Myers RH, Hannan MT, Wilson PW, Ordovas JM, Schaefer EJ, et al. Absence of linkage for bone mineral density to chromosome 12q12–14 in the region of the vitamin D receptor gene. Calcif Tissue Int 2000; 67:434–9.CrossrefGoogle Scholar

  • 15.

    Ye WZ, Reis AF, Velho G. Identification of a novel Tru9 I polymorphism in the human vitamin D receptor gene. J Hum Genet 2000; 45:56–7.CrossrefGoogle Scholar

About the article

Corresponding author: Katerina Zajickova, Institute of Endocrinology, Národní 8, Prague 1, 116 94 Czech Republic Phone: +420-2-24905111; Fax: +420-2-24905325,

Received: 2006-01-12

Accepted: 2006-06-26

Published Online: 2011-09-21

Published in Print: 2006-09-01

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 44, Issue 9, Pages 1066–1069, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2006.204.

Export Citation

©2006 by Walter de Gruyter Berlin New York.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

B Hintzpeter, G B M Mensink, W Thierfelder, M J Müller, and C Scheidt-Nave
European Journal of Clinical Nutrition, 2008, Volume 62, Number 9, Page 1079

Comments (0)

Please log in or register to comment.
Log in