H Jin1, E Evangelou, J P A Ioannidis, S H Ralston. 1. Rheumatic Disease Unit, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh EH42XU, UK.
Abstract
UNLABELLED: A meta-analysis of studies was conducted involving 24,511 participants with 7,864 fractures in which polymorphisms in the 5' flank of COL1A1 (rs1107946, rs2412298, and rs1800012) were related to osteoporosis phenotypes. Polymorphisms of all three sites were associated with BMD, and rs1800012 was associated with fracture but effect sizes were modest. INTRODUCTION AND HYPOTHESIS: Polymorphisms in the 5' flank of COL1A1 gene have been implicated as genetic markers for susceptibility to osteoporosis, but previous studies have yielded conflicting results. METHODS: We conducted a meta-analysis of 32 studies including 24,511 participants and 7,864 fractures in which alleles at the -1997G/T (rs1107946), -1663in/delT (rs2412298), and Sp1 binding site polymorphisms (rs1800012) of COL1A1 had been related to bone mineral density (BMD) or fracture. RESULTS: For the Sp1 polymorphism, BMD values in TT homozygotes were 0.13 units [95% CI, 0.03 to 0.24] lower at the spine (p = 0.01) and 0.16 units [0.10 to 0.23] lower at the hip (p = 1 x 10⁻⁶) than GG homozygotes. Clinical fractures were 1.31-fold [1.04-1.65] increased in TT homozygotes (p = 0.02) and vertebral fractures were 1.34-fold [1.01-1.77] increased (p = 0.04). We also observed associations between spine BMD and allelic variants at the -1997G/T (p = 0.05) and the -1663indelT (p = 0.009) sites. We found no association between alleles at the -1997G/T or -1663indelT sites and fracture but power was limited. CONCLUSIONS: The COL1A1 Sp1 polymorphism is associated with a modest reduction in BMD and an increased risk of fracture, although we cannot fully exclude the possibility that the results may have been influenced by publication bias. Further studies are required to fully evaluate the contribution of the -1997G/T and -1663in/delT sites to these phenotypes and to determine if they interact with the Sp1 polymorphism to regulate susceptibility to osteoporosis.
UNLABELLED: A meta-analysis of studies was conducted involving 24,511 participants with 7,864 fractures in which polymorphisms in the 5' flank of COL1A1 (rs1107946, rs2412298, and rs1800012) were related to osteoporosis phenotypes. Polymorphisms of all three sites were associated with BMD, and rs1800012 was associated with fracture but effect sizes were modest. INTRODUCTION AND HYPOTHESIS: Polymorphisms in the 5' flank of COL1A1 gene have been implicated as genetic markers for susceptibility to osteoporosis, but previous studies have yielded conflicting results. METHODS: We conducted a meta-analysis of 32 studies including 24,511 participants and 7,864 fractures in which alleles at the -1997G/T (rs1107946), -1663in/delT (rs2412298), and Sp1 binding site polymorphisms (rs1800012) of COL1A1 had been related to bone mineral density (BMD) or fracture. RESULTS: For the Sp1 polymorphism, BMD values in TT homozygotes were 0.13 units [95% CI, 0.03 to 0.24] lower at the spine (p = 0.01) and 0.16 units [0.10 to 0.23] lower at the hip (p = 1 x 10⁻⁶) than GG homozygotes. Clinical fractures were 1.31-fold [1.04-1.65] increased in TT homozygotes (p = 0.02) and vertebral fractures were 1.34-fold [1.01-1.77] increased (p = 0.04). We also observed associations between spine BMD and allelic variants at the -1997G/T (p = 0.05) and the -1663indelT (p = 0.009) sites. We found no association between alleles at the -1997G/T or -1663indelT sites and fracture but power was limited. CONCLUSIONS: The COL1A1 Sp1 polymorphism is associated with a modest reduction in BMD and an increased risk of fracture, although we cannot fully exclude the possibility that the results may have been influenced by publication bias. Further studies are required to fully evaluate the contribution of the -1997G/T and -1663in/delT sites to these phenotypes and to determine if they interact with the Sp1 polymorphism to regulate susceptibility to osteoporosis.
Authors: Gregory V Kryukov; Alexander Shpunt; John A Stamatoyannopoulos; Shamil R Sunyaev Journal: Proc Natl Acad Sci U S A Date: 2009-02-06 Impact factor: 11.205
Authors: Yue Fang; Joyce B J van Meurs; Arnold d'Alesio; Mila Jhamai; Hongyan Zhao; Fernando Rivadeneira; Albert Hofman; Johannes P T van Leeuwen; Frédéric Jehan; Huibert A P Pols; André G Uitterlinden Journal: Am J Hum Genet Date: 2005-09-26 Impact factor: 11.025
Authors: V Braga; M Mottes; S Mirandola; V Lisi; G Malerba; L Sartori; G Bianchi; D Gatti; M Rossini; D Bianchini; S Adami Journal: Calcif Tissue Int Date: 2000-11 Impact factor: 4.333
Authors: M Bustamante; X Nogués; A Enjuanes; R Elosua; N García-Giralt; L Pérez-Edo; E Cáceres; R Carreras; L Mellibovsky; S Balcells; A Díez-Pérez; D Grinberg Journal: Osteoporos Int Date: 2006-10-05 Impact factor: 4.507
Authors: V Braga; A Sangalli; G Malerba; M Mottes; S Mirandola; D Gatti; M Rossini; M Zamboni; S Adami Journal: Calcif Tissue Int Date: 2002-05-27 Impact factor: 4.333
Authors: Stuart H Ralston; André G Uitterlinden; Maria Luisa Brandi; Susana Balcells; Bente L Langdahl; Paul Lips; Roman Lorenc; Barbara Obermayer-Pietsch; Serena Scollen; Mariona Bustamante; Lise Bjerre Husted; Alisoun H Carey; Adolfo Diez-Perez; Alison M Dunning; Alberto Falchetti; Elzbieta Karczmarewicz; Marcin Kruk; Johannes P T M van Leeuwen; Joyce B J van Meurs; Jon Mangion; Fiona E A McGuigan; Leonardo Mellibovsky; Francesca del Monte; Huibert A P Pols; Jonathan Reeve; David M Reid; Wilfried Renner; Fernando Rivadeneira; Natasja M van Schoor; Rachael E Sherlock; John P A Ioannidis Journal: PLoS Med Date: 2006-02-21 Impact factor: 11.069
Authors: David Rojano-Mejía; Ramón M Coral-Vázquez; Leticia Cortes Espinosa; Guillermo López-Medina; María C Aguirre-García; Agustín Coronel; Patricia Canto Journal: Age (Dordr) Date: 2011-12-16
Authors: Arseniy M Smirnov; Grigory S Demin; Marina M Mnuskina; Larisa A Scheplyagina; Mikhail M Kostik; Valentina I Larionova Journal: EPMA J Date: 2013-06-13 Impact factor: 6.543