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Osteoporosis International

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13.01.2016 | Original Article

Quantitative genetics of circulating Dickkopf-related protein 1 (DKK1) in community-based sample of UK twins

verfasst von: J. Prakash, F. M. K. Williams, S. Trofimov, G. Surdulescu, T. Spector, G. Livshits

Erschienen in: Osteoporosis International | Ausgabe 6/2016

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Abstract

Summary

Dickkopf-related protein 1 (DKK1) is a major inhibitor of Wnt signalling pathway but also plays an important role in bone formation. Its circulating levels appear to correlate significantly with plasma levels of inflammatory factors, fractalkine and IL-6. This study, using a large sample of UK twins, showed that the variation of each of these factors and correlation between them was explained by the genetic factors, and indicated possible association with DKK1 gene variants.

Introduction

DKK1 is involved in the development of several inflammatory conditions related to bone and joint degradation. Our objectives were to explore the genetic contribution (heritability) to circulating DKK1 variation and its correlation with other inflammatory cytokines, interleukin 6 (IL-6) and fractalkine, and to test whether the DKK1 heritability could be attributable to single nucleotide polymorphisms (SNPs) mapped to DKK1, IL-6 and FRCT genes.

Methods

The study included a large community-based sample of 4939 women drawn from the general UK population. Plasma samples were analysed for circulating levels of DKK1, IL-6 and fractalkine (FRCT); 65 SNPs of DKK1, IL-6 and FRCT candidate genes, with MAF >0.1, were examined. We applied variance component analysis to evaluate contribution of putative genetic (including above SNPs) and environmental factors to variation of DKK1, and its correlation with IL-6 and FRCT.

Results

Putative genetic factors explained 42.2 ± 2 % of the total variation of circulating DKK1 levels, and were also significant for fractalkine and IL-6 variations. Most importantly, we report significant phenotypic (0.208 ± 0.006–0.459 ± 0.007) and genetic (0.338 ± 0.069–0.617 ± 0.033) correlations between these molecules. We found evidence suggestive of association between the DKK1 and its structural genes variants.

Conclusions

Circulating DKK1 levels correlated significantly with levels of IL-6 and FRCT, known risk factors for several inflammatory processes suggesting a potential role of DKK1 in inflammation and tissue injury. Our results suggest the contribution of genetic factors in inter-individual variation of DKK1 levels in human population. However, further studies are required to determine genetic polymorphisms affecting DKK1 variation and its correlation with IL-6 and FRCT.

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Titel: Quantitative genetics of circulating Dickkopf-related protein 1 (DKK1) in community-based sample of UK twins
verfasst von: J. Prakash
F. M. K. Williams
S. Trofimov
G. Surdulescu
T. Spector
G. Livshits
Publikationsdatum: 13.01.2016
Verlag: Springer London
Erschienen in: Osteoporosis International / Ausgabe 6/2016
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-016-3486-x

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Quantitative genetics of circulating Dickkopf-related protein 1 (DKK1) in community-based sample of UK twins

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Results

Conclusions

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