Association Of ENOS Gene Polymorphisms And Avascular Necrosis Of Femoral Head

Back ground:Avascular Necrosis of Femoral Head (ANFH) is a common osteoarticular disease, affecting all age groups, especially young adults between the ages of20and50. The pathological changes of the disease results from multiple environment/genetic risk factors. As a multifunctional biomolecule synthesized by eNOS, NO participate in many physiological process including angiogenesis, thrombosis, coagulation and fibrinolysis. Although some studies of eNOS gene polymorphisms were reported and most of them focus on the27-bp repeat polymorphism in intron4and G894T polymorphism in exon7, few of them is about eNOS gene polymorphisms and ANFH.Objects:By observing association of eNOS polymorphisms and ANFH, we hope to find possible relationship between the ANFH incidence and27-bp repeat polymorphism in intron4and G894T polymorphism in exon7, and to provide scientific basis for further research about the pathogenic mechanism and early diagnosis of the disease.Methods:A total of75atraumatic ANFH patients and75healthy controls without hip trauma history were enrolled. The ANFH gourp were divided into3subgroups:idiopathic, steroid-induced and alcohol-induced. The healthy controls were selected from healthy outpatients to match with ANFH group in age and gendar.Gene polymorphisms in27-bp repeat polymorphism in intron4and G894T polymorphism in exon7were determined. Medical history were collected for etiology analysis.Results:The ANFH group was composed of27male and48female subjects and the mean age was56.4±13.9, while25male and40female patients comprised the healthy control group and the mean age was58.9±11.6. No significant gender or age difference were found between the two groups(p>0.05). Of ANFH group, there are41,13and21samples in idiopathic, steroid-induced and alcohol-induced subgroups, respectively. In the group comparison, the frequency of b/a genotype of intron4in ANFH group is significantly higher than that of the healthy control group (10/75(13.3%) vs.4/75,(5.3%),P=0.0172,OR=3.903), and the result of G/T genotype of exon7also indicates statistical significance between ANFH group and healthy control group (20/75(26.7%) vs.12/75(16.0%), P=0.0345,OR=2.876). In addition, the frequencies of T/T genotype are also different between ANFH and healthy control group(4/75(5.3%),2/75(2.7%),P>0.05), although statistic analysis dose not show significance due to the low population frequency of T/T genotype and the relatively small sample. In subgroup analysis, compared with alcohol-induced group and steroid induced group, genotype b/a are especially higher in idiopathic group than that in healthy control group, while although T/T genotype frequency seems different in the three subgroups, they can’t be analyzed owning to small number of samples.Conclusions:1. eNOS gene polymorphisms is one of the risk factors of ANFH, there is underlying relevance of eNOS and the disease.2. Both27-bp repeat polymorphism in intron4and G894T polymorphism in exon7associates with ANFH incidence.3. Compared between subgroups of different etiology, the idiopathic group is most affected by the two gene polymorphisms.