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Analysis of Association of LRP5, LRP6, SOST, DKK1, and CTNNB1 Genes with Bone Mineral Density in a Slovenian Population

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Abstract

The Wnt pathway has a bifunctional role in bone mass regulation, influencing osteoblasts and osteoclasts. The Wnt pathway genes are therefore candidate genes for susceptibility to osteoporosis. In our study, we focused on the effects of polymorphisms in selected Wnt pathway genes: low-density lipoprotein receptor-related proteins 5 and 6 (LRP5 and LRP6), Dickkopf1 (DKK1), sclerostin (SOST), and β-catenin (CTNNB1). We genotyped 652 subjects for the following polymorphisms: A1330V in LRP5; I1062V in LRP6; E232K in DKK1; D32Y, G34V, and N287S in CTNNB1; and -1397_-1396insGGA in SOST. Bone mineral density (BMD) was also measured. The allele frequencies were as follows: for A1330V C:T = 87%:13%, for I1062V C:T = 20%:80%, and for -1397_-1396insGGA-:GGA = 64%:36%. The studied nucleotide changes in the DKK1 and CTNNB1 genes were shown not to be polymorphic. In a Slovenian population, no association was shown between lumbar spine and femoral neck BMD in A1330V (P = 0.151 and 0.243) and in I1062V (P = 0.209 and 0.405). We observed a difference between SOST genotypes, corresponding to an allele dose effect, which was borderline significant for lumbar spine and femoral neck BMD (P = 0.047 and 0.085); but this did not survive the adjustment for multiple testing. These results indicate that a larger sample size would be necessary to detect these subtle effects. Our results suggest that A1330V in LRP5, I1062V in LRP6, and -1397_-1396insGGA in SOST are not associated with BMD in the Slovenian population.

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Acknowledgement

We are grateful to K. Avbersek, I. Brunskole, S. Jurkovic Mlakar, and Z. Trost for their technical assistance. We thank Prof. Roger Pain for advice on the English language and I. Locatelli for advice on statistical analysis.

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Authors and Affiliations

  1. Faculty of Pharmacy, Department of Clinical Biochemistry, University of Ljubljana, Askerceva cesta 7, 1000, Ljubljana, Slovenia

    Simona Mencej-Bedrač & Janja Marc

  2. Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre, Zaloska cesta 2, SI-1000, Ljubljana, Slovenia

    Janez Preželj & Tomaž Kocjan

  3. Department of Traumatology, General and Teaching Hospital Celje, Celje, Slovenia

    Radko Komadina

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  1. Simona Mencej-Bedrač
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Correspondence to Janja Marc.

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Mencej-Bedrač, S., Preželj, J., Kocjan, T. et al. Analysis of Association of LRP5, LRP6, SOST, DKK1, and CTNNB1 Genes with Bone Mineral Density in a Slovenian Population. Calcif Tissue Int 85, 501–506 (2009). https://doi.org/10.1007/s00223-009-9306-y

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