Necrosis Study PAI-1 Single-nucleotide Polymorphisms And Nontraumatic Femoral Head

Background:Osteonecrosis of femoral head (ONFH) is a bone-destructive disease. Patients are seriously affected with low quality of life due to destruction of bone structures, which eventually leading to femoral head collapse. Epidemiological survey found that the prevalence of ONFH increased significantly in recent years2. Despite great efforts on pathophysiological mechanisms of ONFH research, the exact pathogenesis remains unclear, but the fibrinolytic system disorders are recognized as important risk factor. Study found out that hormones4and alcohol5are risk factors. Within same environment, only some individuals suffered the disease made genetic polymorphism susceptive in pathogenesis of ONFH. In2011, Kim’s study found that SNPs of PAI-1(plasminogen activator inhibitor-1) are associated with ONFH in Korean population15.Objective:1. To identify radios of different ONFH types through epidemiological investigation of ONFH patients enrolled at Beijing Union Medical College Hospital.2. To identify relationship between PAI-1polymorphism and ONFH through candidate SNPs recording to tap SNP and assays published on Pubmed.3. To identify relationship between candidate SNPs and different types of ONFH.4. To verify relationship between rs2227631rs11178and ONFH in Chinese population.Methods:A total of110unrelated patients with clear diagnosis of ONFH and119unrelated control subjects were enrolled at Peking Union Medical College Hospital from2010to2012. Distract DNA from whole blood sample; select candidate SNPs according to Hapmap and assays published on Pubmed; run single base extension reaction to get the target base of SNPs; analyze the target base using MALDI-TOFMS (Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry) depends on molecular weight variations; at last use UNPHASED3.1.5for database analysis.Result:1. PAI-1gene rs11178genotype T/C is related to ONFH in Chineses population as risk factor.2. PAI-1gene rs2227631genotype A/G and G/G are related to ONFH in Chineses population as risk factor.3. PAI-1gene rs2227631rs11178(A-T) haplotype is related to ONFH in Chinese population as protection factor.4. There are no relationship between PAI-1gene rs6950982(A/G) rs2227667(A/G) rs2227672(G/T) rs17135252(A/G) rs6090(A/G) rs2227692(T/C) rs4729664(C/G) rs2227673(A/G) and ONFH in Chinese population based on genotype analysis.5. There are no relationship between PAI-1gene rs11178(C/T) rs6950982(A/G) rs2227667(A/G) rs2227672(G/T) rs17135252(A/G) rs6090(A/G) rs2227692(T/C) rs2227631(A/G) rs4729664(C/G) rs2227673(A/G) and ONFH in Chinese population based on allelic analysis.Conclusion:1. PAI-1gene rs11178genotype T/C is related to ONFH in Chineses population as risk factor.2. PAI-1gene rs2227631genotype A/G and G/G are related to ONFH in Chineses population as risk factor.3. PAI-1gene rs2227631rs11178(A-T) haplotype is related to ONFH in Chinese population as protection factor.4. There are no relationship between all candidate PAI-1SNPs and ONFH in Chinese population based on allelic analysis.