Association of ABCB1 and CYP450 Gene Polymorphisms and their DNA Methylation Status with Steroid-Induced Osteonecrosis of the Femoral Head in the Chinese Population

Osteonecrosis of the femoral head (ONFH) is a severe pathological state with multiple etiologies. Steroid hormone metabolism-related genes play an important role in ONFH. The aim of this study was to investigate the relationships between polymorphisms of the drug-metabolizing enzyme gene, cytochrome P450 ( ), and the drug transporter gene, ATP-binding cassette subfamily B member 1 ( ), as well as their DNA methylation status with the pathogenesis of steroid-induced ONFH. In this case-control study, we evaluated five single nucleotide polymorphisms (SNPs) in two genes in a Han Chinese population, including 79 patients with steroid-induced ONFH and 114 persons who took steroids but did not develop steroid-induced ONFH. SNPs were genotyped by the improved multiplex ligation detection reaction. MethylTarget technology was used to ascertain the methylation status at two CpG islands in the gene for statistical analysis. Finally, interactions between the SNPs and the CpG site's methylation levels were statistically analyzed by methylation quantitative trait locus. We found that the T allele of the rs2242480 locus was associated with steroid-induced ONFH risk reduction (odds ratio [OR] = 0.598, 95% confidence interval [CI]: 0.360-0.992, = 0.046). In the genetic model analysis, the T allele of the rs2032582 locus in the gene was associated with a reduced risk of steroid-induced ONFH under the dominant model (OR = 0.465, 95% CI: 0.223-0.972, = 0.042). The CpG sites with significant differences (