Introduction and Hypothesis: Genetic studies of osteoporosis have analysed single polymorphisms in individual genes with inconclusive results. An alternative approach may involve haplotypes and gene-gene interactions. The aim of the study was to test the association between COLlAl, ESRl, VDR and TGFBl polymorphisms or haplotypes and BMD in Spanish postmeno-pausal women.

Methods: Sixteen polymorphisms were analysed in 719 postmenopausal women. ANOV A, ANCOV A and Xi2 tests were used to perform the statistical analysis.

Results: COLlAl -1997G> T (p=0.04) and TGFBl Leu10Pro (p=0.02) were found to be associated with adjusted lumbar spine BMD (LS BMD). Interactions were observed between: the C0LlAl -1997 Grr and Sp1 polymorphisms (p< 0.0l for LS BMD); and the COLlAl 1663 indelT and VDR ApaI polymorphisms (p< 0.0l for FN BMD). The COLlAl GDs and ESRl LPX haplotypes were associated with FN BMD (p=0.03 and p=0.03).

Conclusion: Polymorphisms at COLlAl and TGFBl and haplotypes at COLlAl and ESRl were associated with BMD in a cohort of postmenopausal Spanish women. Moreover, COLlAl polymorphisms showed significant interactions among them and with the VDR 3’ pol ymorphisms.