J Pepe1,2, N Bonnet3, F R Herrmann4, E Biver3, R Rizzoli3, T Chevalley3, S L Ferrari3. 1. Division of Bone Diseases, Faculty of Medicine, Geneva University Hospitals, 1205, Geneva, Switzerland. jessica.pepe@uniroma1.it. 2. Department of Internal Medicine and Medical Disciplines, "Sapienza" University of Rome, Viale del Policlinico 155, 00161, Rome, Italy. jessica.pepe@uniroma1.it. 3. Division of Bone Diseases, Faculty of Medicine, Geneva University Hospitals, 1205, Geneva, Switzerland. 4. Division of Geriatrics, Department of Internal Medicine, Rehabilitation and Geriatrics, Geneva University Hospitals, University of Geneva, Geneva, Switzerland.
Abstract
We investigated the interaction between periostin SNPs and the SNPs of the genes assumed to modulate serum periostin levels and bone microstructure in a cohort of postmenopausal women. We identified an interaction between LRP5 SNP rs648438 and periostin SNP rs9547970 on serum periostin levels and on radial cortical porosity. PURPOSE: The purpose of this study is to investigate the interaction between periostin gene polymorphisms (SNPs) and other genes potentially responsible for modulating serum periostin levels and bone microstructure in a cohort of postmenopausal women. METHODS: In 648 postmenopausal women from the Geneva Retirees Cohort, we analyzed 6 periostin SNPs and another 149 SNPs in 14 genes, namely BMP2, CTNNB1, ESR1, ESR2, LRP5, LRP6, PTH, SPTBN1, SOST, TGFb1, TNFRSF11A, TNFSF11, TNFRSF11B and WNT16. Volumetric BMD and bone microstructure were measured by high-resolution peripheral quantitative computed tomography at the distal radius and tibia. RESULTS: Serum periostin levels were associated with radial cortical porosity, including after adjustment for age, BMI, and years since menopause (p = 0.036). Sixteen SNPs in the ESR1, LRP5, TNFRSF11A, SOST, SPTBN1, TNFRSF11B and TNFSF11 genes were associated with serum periostin levels (p range 0.03-0.001) whereas 26 SNPs in 9 genes were associated with cortical porosity at the radius and/or at the tibia. WNT 16 was the gene with the highest number of SNPs associated with both trabecular and cortical microstructure. The periostin SNP rs9547970 was also associated with cortical porosity (p = 0.04). In particular, SNPs in LRP5, ESR1 and near the TNFRSF11A gene were associated with both cortical porosity and serum periostin levels. Eventually, we identified an interaction between LRP5 SNP rs648438 and periostin SNP rs9547970 on serum periostin levels (interaction p = 0.01) and on radial cortical porosity (interaction p = 0.005). CONCLUSION: These results suggest that periostin expression is genetically modulated, particularly by polymorphisms in the Wnt pathway, and is thereby implicated in the genetic variation of bone microstructure.
We investigated the interaction between periostin SNPs and the SNPs of the genes assumed to modulate serum periostin levels and bone microstructure in a cohort of postmenopausal women. We identified an interaction between LRP5 SNP rs648438 and periostin SNP rs9547970 on serum periostin levels and on radial cortical porosity. PURPOSE: The purpose of this study is to investigate the interaction between periostin gene polymorphisms (SNPs) and other genes potentially responsible for modulating serum periostin levels and bone microstructure in a cohort of postmenopausal women. METHODS: In 648 postmenopausal women from the Geneva Retirees Cohort, we analyzed 6 periostin SNPs and another 149 SNPs in 14 genes, namely BMP2, CTNNB1, ESR1, ESR2, LRP5, LRP6, PTH, SPTBN1, SOST, TGFb1, TNFRSF11A, TNFSF11, TNFRSF11B and WNT16. Volumetric BMD and bone microstructure were measured by high-resolution peripheral quantitative computed tomography at the distal radius and tibia. RESULTS: Serum periostin levels were associated with radial cortical porosity, including after adjustment for age, BMI, and years since menopause (p = 0.036). Sixteen SNPs in the ESR1, LRP5, TNFRSF11A, SOST, SPTBN1, TNFRSF11B and TNFSF11 genes were associated with serum periostin levels (p range 0.03-0.001) whereas 26 SNPs in 9 genes were associated with cortical porosity at the radius and/or at the tibia. WNT 16 was the gene with the highest number of SNPs associated with both trabecular and cortical microstructure. The periostin SNP rs9547970 was also associated with cortical porosity (p = 0.04). In particular, SNPs in LRP5, ESR1 and near the TNFRSF11A gene were associated with both cortical porosity and serum periostin levels. Eventually, we identified an interaction between LRP5 SNP rs648438 and periostin SNP rs9547970 on serum periostin levels (interaction p = 0.01) and on radial cortical porosity (interaction p = 0.005). CONCLUSION: These results suggest that periostin expression is genetically modulated, particularly by polymorphisms in the Wnt pathway, and is thereby implicated in the genetic variation of bone microstructure.
Entities:
Keywords:
Bone microstructure; Heritability; LRP5; Periostin; SNPs
Authors: Anne-Marie Sims; Neil Shephard; Kim Carter; Tracy Doan; Alison Dowling; Emma L Duncan; John Eisman; Graeme Jones; Geoffrey Nicholson; Richard Prince; Ego Seeman; Gethin Thomas; John A Wass; Matthew A Brown Journal: J Bone Miner Res Date: 2008-04 Impact factor: 6.741
Authors: Lavinia Paternoster; Mattias Lorentzon; Terho Lehtimäki; Joel Eriksson; Mika Kähönen; Olli Raitakari; Marika Laaksonen; Harri Sievänen; Jorma Viikari; Leo-Pekka Lyytikäinen; Dan Mellström; Magnus Karlsson; Osten Ljunggren; Elin Grundberg; John P Kemp; Adrian Sayers; Maria Nethander; David M Evans; Liesbeth Vandenput; Jon H Tobias; Claes Ohlsson Journal: PLoS Genet Date: 2013-02-21 Impact factor: 5.917
Authors: Stephanie Boutroy; Sundeep Khosla; Elisabeth Sornay-Rendu; Maria Belen Zanchetta; Donald J McMahon; Chiyuan A Zhang; Roland D Chapurlat; Jose Zanchetta; Emily M Stein; Cesar Bogado; Sharmila Majumdar; Andrew J Burghardt; Elizabeth Shane Journal: J Bone Miner Res Date: 2016-06 Impact factor: 6.741
Authors: Nicolas Bonnet; Emmanuel Biver; Thierry Chevalley; René Rizzoli; Patrick Garnero; Serge L Ferrari Journal: J Bone Miner Res Date: 2017-08-02 Impact factor: 6.741
Authors: S L Ferrari; B Abrahamsen; N Napoli; K Akesson; M Chandran; R Eastell; G El-Hajj Fuleihan; R Josse; D L Kendler; M Kraenzlin; A Suzuki; D D Pierroz; A V Schwartz; W D Leslie Journal: Osteoporos Int Date: 2018-07-31 Impact factor: 4.507