Genetic association study of polymorphisms in the catalase gene with the risk of osteonecrosis of the femoral head in the Korean population.

Osteonecrosis (ON) of the femoral head frequently leads to progressive collapse of the femoral head followed by degenerative arthritis of the hip joint. Oxidative stress, which has been implicated in many pathological conditions, including vascular injury, recently has been suggested to play a part in the development of ON. Catalase (CAT) is a major antioxidant enzyme and a number of polymorphisms in the CAT have been described as being associated with several diseases, such as hypertension, diabetes mellitus, Alzheimer's disease, and vitiligo. The aim of this study was to evaluate the association of CAT gene polymorphisms with ON of the femoral head (ONFH) in a case-control study.Eight polymorphic sites of CAT were selected from public databases, and genotyped in 443 ONFH patients and 273 control subjects using the Affymetrix Targeted Genotyping (TG) 3K chip array. The association analysis of genotyped single nucleotide polymorphisms (SNPs) and haplotypes was performed with ONFH.The -89A>T, -20T>C, +3033C>T, +14539A>T, +22348C>T, and +24413T>C polymorphisms of the CAT gene were significantly associated with the risk of ONFH in all alternative analysis models (P range; 0.0001-0.035, odds ratio [OR]: 0.52-3.47). Particularly, the minor allele of -89A>T, -20T>C and +3033C>T had a protective effect on ONFH with significance (P range: 0.0014-0.035, OR: 0.52-0.73). Further analysis based on pathological etiology showed that the genotypes of -89A>T, -20T>C, +3033C>T, +14539A>T, and +22348C>T, and +24413T>C were also associated with the risk of ONFH in each subgroup with significant P values.These findings indicate that the polymorphisms of CAT are associated with the ONFH, and suggest that oxidative stress may play an important role in the pathogenesis of ONFH.