The reduction in the expression or activity of eNOS could result in lower production of NO and subsequent abnormalities in vascular reactivity, platelet recruitment, angiogenesis, bone 
volume, and bone formation rate. It has been demonstrated that two polymorphic sites of the eNOS gene, the 27-bp repeat polymorphism in intron 4 and G894T polymorphism in exon 7, are Gentiopicrin associated with the altered function of this gene. A study in Korean patients demonstrated that polymorphism in intron 4 of eNOS was significantly associated with idiopathic femur head osteonecrosis, but the distribution of G894T polymorphisms was not significantly different between patients and controls. The T786C polymorphism is related to the G894T polymorphism and was also reported to be associated with eNOS gene function. Glueck et al. study in Caucasian and African American patients demonstrated that the T786C eNOS polymorphism and resultant reduction of nitric oxide production are associated with the pathogenesis of idiopathic ANFH. Although only a few studies investigated the association of eNOS polymorphism with the pathogenesis of ANFH, the effects of genetic differences between populations and confounders could not be excluded. Currently, no report has investigated the association between eNOS polymorphisms and pathogenesis of ANFH in Chinese patients. In this study, we investigated the 27-bp repeat polymorphism in intron 4 and G894T polymorphism in exon 7 of the eNOS gene in 125 Chinese patients with non-traumatic ANFH and evaluated ANFH according to the etiologic factors. Although non-traumatic ANFH has been widely recognized as a pathological state with multiple etiologies, the exact pathogenesis of Rosiridin osteonecrosis remains to be elucidated. Chronic steroid use and alcoholism were thought to be the main risk factors for osteonecrosis. Recent research has explored associations between genetic mutations, polymorphisms, and pathogenesis of ANFH. Single nucleotide polymorphisms in the multidrug resistance gene have been revealed to be associated with corticosteroid-induced osteonecrosis. Genetic variation of alcohol-metabolizing enzyme genes has been associated with alcoholism-induced osteonecrosis. Polymorphism in intron 4 and T786C polymorphism of eNOS were found to be significantly associated with idiopathic ANFH. In this study, we demonstrated that the frequency of 4a allele, b/a genotype in intron 4 and allele 894T, GT genotype in exon 7 were significantly higher in idiopathic subgroup of ANFH patients than in healthy controls. It has been demonstrated that the presence of 27-bp repeat polymorphism in intron 4 and G894T polymorphism in exon 7 could result in a change in eNOS expression and enzymatic activity. For example, plasma NO levels in subjects with the 4a allele of eNOS were significantly lower than those without the 4a allele. eNOS isoforms are processed differently within the cell depending on the presence of aspartate or glutamate at position 298 of the eNOS protein. Therefore, 4a and G894T gene polymorphisms can lead to low expression and activity of eNOS. Koo et al study in Korean patients demonstrated that the frequency of 4a allele and 4a/b genotype was significantly higher in femoral head osteonecrosis patients and idiopathic subgroup of FHON patients compared to healthy controls. In contrast, the distribution of G894T polymorphisms was not significantly associated with FHON. Consistent with the study in Korean patients, we observed that the frequency of 4a allele and 4a/b genotype was significantly higher in ANFH patients, especially in idiopathic osteonecrosis patients than in controls. In contrast, our study revealed that G894T polymorphism was significantly higher in ANFH patients as well as idiopathic osteonecrosis patients compared to controls.