Association of collagen I alpha 1 Sp1 polymorphism with the risk of prevalent fractures: A meta-analysis

Several studies have addressed the effect of the Sp1 polymorphism of the co llagen I alpha 1 (COLIA1) gene on the prevalence of fractures. The results are not in full agreement on whether this polymorphism is associated with f racture risk. To clarify this uncertainty, we performed a meta-analysis inc luding 13 eligible studies with 3641 subjects. The COLIA1 Sp1 polymorphism showed a dose-response relationship with the prevalence of fractures. The r isk was 1.25-fold (95% Cl, 1.09-1.45) in Ss heterozygotes versus SS homozyg otes, 1.68-fold (95% CI, 1.35-2.10) in ss homozygotes versus SS homozygotes , and 1.35 (95% Cl, 1.04-1.75) for ss homozygotes versus Ss heterozygotes b y random effects calculations. There was modest heterogeneity for these thr ee effect estimates (p value for heterogeneity, 0.17, 0.16, and 0.08, respe ctively). The Spl polymorphism effects possibly were larger when the analys is was limited to studies considering only vertebral fractures (pooled risk ratios [RR], 1.30, 2.07, and 1.46, respectively). Conversely, the Sp 1 pol ymorphism effects tended to be smaller in studies with mean patient age gre ater than or equal to 65 years than in studies with younger patients on ave rage, but the differences were not formally significant. We estimated the t otal average attributable fraction (AF) of fractures due to the s allele in European/U.S. populations as 9.4%. The meta-analysis suggests an important role for the Sp1 polymorphism in the regulation of fracture risk; however, potential heterogeneity across ethnic groups, age groups, and skeletal sit es may be important to clarify in future studies. Very large studies or met a-analyses are required to document subtle genetic differences in fracture risk.