ECTS2016 Poster Presentations Genetics and Epigenetics (25 abstracts)
1Division of Bone Diseases, University Hospitals and Faculty of Medicine, Geneva, Switzerland; 2Department of Internal Medicine and Medical Disciplines, Sapienza University, Rome, Italy; 3Division of Geriatrics, Department of Internal Medicine, Rehabilitation and Geriatrics, University Hospitals, Geneva, Switzerland.
Background: Periostin is a matricellular protein involved in bone modeling and remodeling through the modulation of WNT-β catenin signaling in osteoblasts and osteocytes.
Aim: To investigate the interaction between polymorphisms of six periostin SNPs and other gene polymorphism involved in periostin expression and activity on periostin serum levels and bone microarchitecture in a cohort of postmenopausal women.
Methods: A total of 648 postmenopausal women from the Geneva Retirees Cohort (GERICO) were analyzed for six periostin SNPS (rs9547952, rs9603226, rs7322993, rs9576308, rs7338244, rs9547970) and for several SNPs in BMP2, CTNNB1, ESR 1, ESR 2, LRP5, LRP6, PTH, PTH R, SPTBN1, SOST, TGF B, TNFRSF11A and WNT 16. Periostin serum levels were determined by ELISA. Distal radius, tibia volumetric BMD and bone microstructure were measured by high-resolution peripheral quantitative computed tomography (XtremCT, Scanco Co, Bruttisellen, CH). Two ways ANOVA was carried out to assess the SNPs effects and their interaction on cortical porosity or periostin serum levels.
Results: ESR1 SNP rs851982, LRP5 SNP rs648438 and TNFRSF11A SNP rs2957137 were associated with periostin serum levels (P values range 0.030.0004) as well as with cortical porosity (P values range 0.040.005). Periostin SNP rs9547970 was also associated with cortical porosity at radius and tibia (P=0.04).
Furthermore, we identified an interaction between LRP5 SNP 648438 and periostin SNP rs9547970 on radial cortical porosity (P=0.005), and on periostin serum level (P=0.01). In particular, lower periostin serum levels and higher cortical porosity were associated with periostin SNP 954790 GG and LRP5 SNP rs648438 CC and CT.
Conclusion: Gene polymorphism in the estrogen receptor, WNT and RANK pathway are associated with serum periostin levels and cortical microstructure. LRP5 interacts also with Postn polymorphism on bone microstructure. If confirmed in independent cohort, these data confirm the complexity of genetic determinant of bone fragility that involves periostin.