Population-Based Studies Of Genetic Variants Of Frzb With Osteoarthritis At Three Joint Sites: A Comprehensive Meta-Analysis

To address the ambiguities raised by inconsistent results among molecular genetic studies between the rs288326 (R200W) and rs7775 (R324G) variants of the FRZB gene and osteoarthritis (OA), we synthesized standardized data on hip, knee, and hand OA according to a common meta-analysis protocol. There were nine independent case-control studies that were candidates for performing an association analysis of the SNPs rs288326 and rs7775 in the FRZB locus of patients with OA at three joint sites. For SNP rs288326, the case and control sample sizes were 3,803 and 5,972 for hip OA, 2,305 and 2,514 for knee OA, and 2,761 and 1,463 for hand OA, respectively, and for SNP rs7775, the case and control sample sizes were 3,849 and 8,843 for hip OA, 2,315 and 2,506 for knee OA, and 2,796 and 1,456 for hand OA, respectively. Using a fixed-effect model, the summary effect for the T-allele of rs288326 was statistically significant in females with knee OA between patients and controls (Subtotal OR=1.24, 95% CI=1.01-1.53, Z=2.02, P=0.04), and an association trend was revealed for this SNP in females with hip OA (Subtotal OR=1.12, 95% CI=0.99-1.28, Z=1.75, P=0.08). In summary, our study supports the hypothesis that FRZB may play a small but important role in the pathogenesis of OA in females, at least in females with hip OA or knee OA. Further gender-based studies are needed to elucidate the actual role of FRZB in the physiology of human bone and cartilage and in the pathogenesis of skeletal disorders.