Context and Objective. Hip fracture is partially genetically determined. The present study was designed to examine the contributions of VDR and COLIA1 genotypes to the liability to hip fracture in postmenopausal women.

Design. Prospective population based cohort.

Subjects. 677 postmenopausal women of Caucasian background, aged 70 ± 7 yr (mean±SD) have been followed for up to 14 yr. Sixty-nine women had sustained a hip fracture during the period.

Main outcome. Atraumatic hip fractures were prospectively identified through radiologists' reports. BMD at the hip and lumbar spine was measured by dual energy x-ray absorptiometry.

Genotypes. The Taq-1 and Sp-1 COLIA1 polymorphisms of the VDR and COLIA1 genes were determined. Using SNP database, VDR TT, Tt and tt genotypes were coded as TT, TC and CC, while COLIA1 SS, Ss and ss were coded as GG, GT and TT.

Results. Women with VDR CC genotype (16% prevalence) and COLIA1 TT genotype (5% prevalence) had an increased risk of hip fracture (odds ratio [OR] associated with CC: 2.6; 95%CI: 1.2-5.3, OR associated with TT: 3.8; 95% CI: 1.3-10.8) after adjustment for femoral neck BMD (OR: 3.4 per SD 95%CI: 2.3-5.0) and age (OR: 1.4 per 5 yr; 95%CI: 1.1-1.7). Approximately 20% and 12% of the liability to hip fracture was attributable to the presence of the CC genotype and TT genotype, respectively.

Conclusion. The VDR CC genotype and COLIA1 TT genotype were associated with increased hip fracture risk in Caucasian women and this association was independent of BMD and age.