Bustamante M, Nogués X, Enjuanes A, Elosua R, García-Giralt N, Pérez-Edo L, Cáceres E, Carreras R, Mellibovsky L, Balcells S, Díez-Pérez A, Grinberg D
Department of Genetics, Universitat de Barcelona, Barcelona, Spain.
Osteoporos Int. 2007 Feb;18(2):235-43. doi: 10.1007/s00198-006-0225-8. Epub 2006 Oct 5.
Genetic studies of osteoporosis have focused on analysing 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 the COL1A1, ESR1, VDR and TGFB1 polymorphisms or haplotypes and bone mineral density (BMD) in Spanish postmenopausal women.
Sixteen polymorphisms were analysed in 719 postmenopausal women. ANOVA, ANCOVA and Xi2 tests were used to perform the statistical analysis.
COL1A1 -1997G > T (p=0.04) and TGFB1 Leu10Pro (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).
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 significant interactions among them and with the VDR 3' polymorphisms.
骨质疏松症的基因研究主要集中在分析单个基因中的单核苷酸多态性——结果尚无定论。另一种方法可能涉及单倍型和基因-基因相互作用。本研究的目的是检测西班牙绝经后女性中COL1A1、ESR1、VDR和TGFB1基因多态性或单倍型与骨密度（BMD）之间的关联。
对719名绝经后女性的16种多态性进行了分析。采用方差分析、协方差分析和卡方检验进行统计分析。
发现COL1A1 -1997G>T（p=0.04）和TGFB1 Leu10Pro（p=0.02）与调整后的腰椎（LS）骨密度相关。观察到以下基因之间存在相互作用：COL1A1 -1997 G/T和Sp1多态性（腰椎骨密度p<0.01）以及COL1A1 -1663 indelT和VDR ApaI多态性（股骨颈（FN）骨密度p<0.01）。COL1A1 GDs和ESR1 LPX单倍型与股骨颈骨密度相关（p=0.03和p=0.03）。
在一组西班牙绝经后女性中，发现COL1A1和TGFB1基因的多态性以及COL1A1和ESR1基因的单倍型与骨密度相关。此外，COL1A1基因多态性之间以及与VDR 3'多态性之间存在显著的相互作用。
