Vascular endothelial growth factor polymorphisms in patients with steroid-induced femoral head osteonecrosis

To investigate an association between steroid-induced femoral head osteonecrosis (FHON) and functional vascular endothelial growth factor (VEGF) gene (-2578A/C, -1154A/G, -634C/G, and +405C/G) polymorphisms polymerase chain reaction-restriction fragment length polymorphism genotyping was performed in 160 patients (86 idiopathic FHON and 74 steroid-induced FHON) and 160 gender- and age-matched controls. The steroid-induced subgroup had a significantly lower prevalence of -1154A allele (7.4% vs. 18.1%, odds ratio (OR) = 0.363) and genotype carrying -1154A (14.9% vs. 32.5%, OR = 0.333 in a recessive model) than controls. In a dominant model, the frequency of genotype carrying +405G (74.3% vs. 84.4%, OR = 0.492) was significantly lower in steroid-induced FHON than in controls. The distribution of haplotypes was significantly different between controls and FHON patients (p = 0.00011). Especially, when haplotypes were classified into high (CGCG and AAGG) or low (CGGC and AGGC) VEGF inducing haplotypes, patients with steroid-induced FHON had a significantly lower prevalence of high inducing haplotypes (7.4% vs. 15.9%, OR = 0.424) and a significantly higher prevalence of low inducing haplotypes (4.7% vs. 0.6%, OR = 7.894) than controls. Low inducing VEGF haplotypes may confer an increased risk and high inducing haplotypes have a protective effect for the development of steroid-induced FHON in Korea.