Association Between Catenin Beta-1 (CTNNB1) Gene Polymorphisms and Non-Traumatic Osteonecrosis of the Femoral Head (ONFH)

Non-traumatic osteonecrosis of the femoral head (ONFH) is a multifactorial disorder in which genetic susceptibility is thought to play an important role, yet the contribution of many candidate genes remains unclear. The catenin beta-1 (CTNNB1) gene encodes β-catenin, a key regulator of the Wnt/β-catenin signaling pathway involved in bone homeostasis and vascular regulation, and may therefore influence susceptibility to non-traumatic ONFH. In this case-control study, genotype data from China Medical University Hospital were analyzed to evaluate the association between CTNNB1 polymorphisms and the risk of ONFH. A total of 609 patients with ONFH and 2436 age- and sex-matched controls were included. Fourteen CTNNB1 single-nucleotide polymorphisms (SNPs) with a minor allele frequency greater than 5% were selected and analyzed using logistic regression under multiple genetic models, with Hardy-Weinberg equilibrium assessed in controls. Two SNPs, rs3774370 and rs11564478, showed significant differences in allele frequencies between cases and controls, with lower minor allele frequencies observed in the ONFH group. Both variants were associated with a reduced risk of ONFH, and these associations remained significant under dominant genetic models. These findings suggest that specific CTNNB1 polymorphisms may confer a protective effect against non-traumatic ONFH and provide further insight into the genetic architecture of this disease.