Association Between Genetic Polymorphisms of CR2 Gene and the Risk of Steroid-Induced Osteonecrosis of the Femoral Head in the Chinese Han Male Population.

Background: Multiple lines of evidence have suggested that genetic factors may contribute to steroid-induced osteonecrosis of the femoral head (SONFH). Complement receptor 2 (CR2), constituting a family of regulators of complement activation, has been recently reported to be associated with osteonecrosis of the femoral head (ONFH) in Koreans. The aim of this study was to evaluate the relationships between the CR2 gene and susceptibility to SONFH in the male Han Chinese population. Materials and Methods: A total of 468 SONFH patients and 1224 healthy controls were recruited to the study. Ten tag single nucleotide polymorphisms (SNPs) located within the CR2 gene were genotyped. Genetic association analyses, including SNP and haplotypic analyses, were performed for the 10 SNPs. Furthermore, bioinformatic analyses were conducted to examine the functional consequences of significant SNPs. Results: An intronic SNP, rs311306, was identified to be significantly associated with the risk of SONFH (p = 0.0008, odds ratio = 1.44). Allelic analyses showed that the C allele of this SNP significantly elevated the risk of SONFH, which was replicated in genotypic association analyses. Moreover, a 3-SNP haplotype was significantly associated with SONFH (rs311306-rs17044576-rs3767933, p = 7.49 × 10-8). Furthermore, bioinformatic analysis results indicated limited functional consequences of SNP rs311306, but a complex interaction network was constructed by the protein encoded by the SLC44A2 gene and proteins encoded by CD19, CD81, and C3 genes. Conclusion: Our findings shed new light on the link between the CR2 gene and SONFH in Han Chinese males, providing clues as to the nature of the mechanisms involved in the etiology of ONFH.