Studies of COLIA1 alleles in the pathogenesis and treatment of osteoporosis : a summary
Collagen is the major protein of bone, and an intronic polymorphism of the COLIA1 gene is associated with low bone mineral density (BMD) and with osteoporotic vertebral fracture. This polymorphism has not been extensively studied in hip fracture. We screened a cohort of 661 females with osteoporotic hip fracture in comparison with 483 controls, and carried out a similar analysis in 169 males. Genotyping was carried out for the COLIA1 sp1 and VDR Bsm1 polymorphisms. The COLIA 1 Sp1 polymorphism was found to be an independent risk factor for hip fracture among females, with 'ss' homozygotes being at increased risk (OR=2.772; 95% CI: 1.11-693; p=0.031). No such difference was seen in relation to VDR genotype. Hip geometry is a risk factor for hip fracture. We investigated the relationship between COLIA1 Sp1 alleles and femoral neck geometry by carrying out measurements in pelvic radiographs from 153 patients with hip fracture, and in DXA scan printouts from 183 normal subjects. While no difference was seen between hip axis length and femoral neck width between COLIA1 genotypes, a wider femoral neck angle (approx. 2°) was seen in individuals expressing the 's' allele (p=0.001; GLM ANOVA). Such an increase in angle may have unfavourable biomechanical consequences in the event of a fall. We also investigated the effect of etidronate therapy on BMD in relation to COLIA1 genotype in a cohort of 108 post-menopausal women using a randomised-controlled trial. Individuals expressing the 's' allele had a heterogeneous BMD response at the hip as compared with 'SS' homozygotes. In general 'Ss' heterozygotes responded poorly to etidronate at the hip, but this differential response was not seen at the lumbar spine. The COLIA1 Sp1 polymorphism thus has complex effects on the structure and function of bones as studied at the femoral neck.