Background:
Polymorphisms in the collagen type Iα1 (COLIA1) gene is associated with bone mineral density (BMD), but its association with bone loss remains unknown. This study sought to test the hypothesis that COLIA1 polymorphisms are associated with both bone loss and fracture risk.
Methods:
The study involved 809 postmenopausal women in the Dubbo Osteoporosis Epidemiology Study. The women's bone health has been monitored for up to 30 years. BMD at the lumbar spine (LSBMD) and femoral neck (FNBMD) was biennially measured by DXA (GE-Lunar Prodigy). Fragility fracture was ascertained by X-ray reports. The G->T polymorphism at the Sp1 binding site in the COLIA1 gene was determined by the PCR-based method. The association between COLIA1 genotypes and bone loss was analysed by the mixed-effects model. The contribution of COLIA1 genotypes to fracture risk was analysed by the Cox’s regression model.
Results:
The distribution of COLIA1 genotypes was consistent with the Hardy-Weinberg's equilibrium law: TT (n=31; 3.8%), GT (n=256; 32%) and GG (n=522; 64.2%). The rate of bone loss was -0.85±2.03%, -0.58+1.55% and -0.56+1.39% per year for women with TT, GT and GG genotype, respectively (p=0.57). During a median follow-up of 18.3 years, there were 423 fragility fractures, including 120 hip fractures. Women with TT genotype were associated with an increased risk of any fracture (adjusted HR: 2.16; 95%CI: 1.40-3.32) and hip fracture (adjusted HR=3.73; 95%CI, 1.84-7.56) than women with GG/GT genotype.
Conclusion:
These data suggest that polymorphic variation at the COLIA1 gene is not associated with bone loss, but associated with fracture risk, independent of BMD. This finding suggests that the COLIA1 gene may be a useful predictor of osteoporotic fracture in the elderly population.