ORIGINAL ARTICLE COL1A1, ESR1, VDR and TGFB1 polymorphisms and haplotypes in relation to BMD in Spanish postmenopausal women 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 Received: 21 April 2006 / Accepted: 28 August 2006 / Published online: 5 October 2006 # International Osteoporosis Foundation and National Osteoporosis Foundation 2006 Abstract Introduction and hypothesis Genetic studies of osteoporo- sis have focused on analysing single polymorphisms in individual genes – with inconclusive results. An alternative approach may involve haplotypes and gene-gene interac- tions. The aim of the study was to test the association between the COL1A1, ESR1, VDR and TGFB1 polymor- phisms or haplotypes and bone mineral density (BMD) in Spanish postmenopausal women. Methods Sixteen polymorphisms were analysed in 719 postmenopausal women. ANOVA, ANCOVA and Xi 2 tests were used to perform the statistical analysis. Results COL1A1 -1997G>T (p =0.04) and TGFB1 Leu10- Pro (p =0.02) were found to be associated with adjusted lumbar spine (LS) BMD. Interactions were observed between: the COL1A1 -1997 G/T and Sp1 polymorphisms (p <0.01 for LS BMD) and the COL1A1 -1663 indelT and VDR ApaI polymorphisms (p <0.01 for femoral neck (FN) BMD). The COL1A1 GDs and ESR1 LPX haplotypes were associated with FN BMD (p =0.03 and p =0.03). Conclusions Polymorphisms at COL1A1 and TGFB1 and haplotypes at COL1A1 and ESR1 were found to be associated with BMD in a cohort of postmenopausal Spanish women. Moreover, COL1A1 polymorphisms showed sig- nificant interactions among them and with the VDR 3′ polymorphisms. Keywords Association studies . BMD . Collagen . Haplotype . Interaction . Polymorphism Introduction Genetics is a critical factor in osteoporosis development. There have been a considerable number of important findings in this field, and several polymorphisms have been related with skeletal health. However, the genetic basis of the disease is still poorly understood. Morrison et Osteoporos Int (2007) 18:235–243 DOI 10.1007/s00198-006-0225-8 M. Bustamante : N. García-Giralt : S. Balcells : D. Grinberg Department of Genetics, Universitat de Barcelona, Barcelona, Spain X. Nogués : A. Enjuanes : L. Mellibovsky : A. Díez-Pérez Internal Medicine, URFOA, IMIM, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain R. Elosua URLEC, URFOA, IMIM, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain L. Pérez-Edo Department of Rheumatology, URFOA, IMIM, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain E. Cáceres Department of Traumatology and Orthopedics, URFOA, IMIM, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain R. Carreras Department of Obstetrics and Gynecology, URFOA, IMIM, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain D. Grinberg (*) Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Av. Diagonal, 645, 08028 Barcelona, Spain e-mail: dgrinberg@ub.edu