The Study Of Monocyte Chemoattractant Protein-1on The Occurrence And Development Of Spinal Tuberculosis

Chapter1The study of the eorrelation between human monoeyte chemoattaetant protein-1promoter vatiant-2518, vatiant-362and susceptibility to spinal tubereulosisObjective:To investigate the relationship between monocyte chemoattactant protein-1gene promoter variant-2518,variant-362and susceptibility to spinal tuberculosis in Hunan Han population.Method:332patients with spinal tuberculosis(sTB),334patients with pulmonary tuberculosis(pTB)and336healthy controls were recruited in our study from December2004to December2010.The MCP-1promoter polymorphisms at position-2518and-362were detected by polymerase chain reaction and direct DNA sequencing.The genotyPes and alleles fequency were analyzed by Statistic and the relationship between them and susceptibility to tuberculosis is evaluated.Results:Gender,MCP-1promoter variant-2518and variant-362C are associated with sysceptibility to spinal tuberculosis and they work in synergistic effect. Male(χ2=6.806,OR=1.519,95％CI=1.110-2.079),-2518GG genotypes(χ2=16.656,OR=2.771,95％CI=1.698-4.52),-362-CC genotypes(χ2=11.802,OR=2-188,95％CI=1.4-3.421), and-362-GC genotypeS (χ2=10.141,OR=2.014,95％CI=1.309-3.1)were associated with increased spinal TB susceptibility respectively in Hunan Han population.Male patients whi have bith-2518-GG and-362-CC genotypes are most susceptible to sTB (χ2=5.053, OR=5.537,95％CI=1.237-23.208).Female patients who have both-2518-GG and一362一CC genotYPes(χ2=9.208,OR=8.8,95％CI=2.16-35.853)or一362一GC genotypes(χ2=7.061,OR=7.273,95％CI=1.683-31.427)are more susceptible to sTB.pTB patients with-2518-GG genotypes are more likely to progtess to sTB(χ2=4.780,OR=1.722,95％CI=1.058-2.803)especially female pTB patients who have both-2518-GG and-362-CC genotypes are most likely to progtess to sTB(χ2=5.637OR=5.867,95％CI=1362-25.275). Conclusion:(1)The'first research in China to investigate the relationship between the MCP-1promoter variant-2518and variant-362and the susceptibility to spinal tuberculosis. Male, MCP-1-2518GG and MCP-1-362-CC/GC genotypes were associated with increased spinal TB susceptibility and conjunctively.(2)Pulmonary tuberculosis patients who have MCP-1-2518-GG genotypes are more likely to progress to spinal tuberculosis especially female pulmonary tuberculosis patients who have both MCP-1-2518-GG and MCP-1-362-CC genotypes are most likely to progress to spinal tuberculosis. This study provid genetics theoretical basis for a prevention and early diagnosis of spinal tuberculosis in clinical work.Chapter2The study to the influence factors of serumMCP-1expression and the relationship between serum MCP-1concentration and development of spinal tuberculosisObjective:To analysis the influence factors of serum MCP-1expression. And to explore the association between serum MCP-1concentration and development of spinal tuberculosis.Method:332spinal tuberculosis patients,334pulmonary tuberculosis patients and336healthy controls were recruited in our study from December2004to December2010. Their serum MCP-1concentration were detected by enzyme linked immunosorbent assay (ELISA). Analysis the influence factors of serum MCP-1expression, explore the association between serum MCP-1concentration and development of spinal tuberculosis combined with MCP-1genotype s which detected before.Results:Both of the MCP-1-2518-GG genotype (F=5.52,p=0.006) and MCP-1-362-CC genotype (F=4.982, p=0.01) were associated with increased serum MCP-1concentrations. And combination of these two genotypes are parallel to the most high level serum MCP-1concentration(F=15.848, p<0.001). Serum MCP-1concentrations are in a gradually rising trend as the tuberculosis progresses (F=18.11, p<0.001). In spinal tuberculosis patients, the mean serum MCP-1concentration was154.44±68.81pg/ml. It was significantly higher than pulmonary patients'(102.58±59.29pg/ml) and normal controls'(36.69±21.71pg/ml). Serum MCP-1concentrations can be used as serological markers for clinical diagnosis of tuberculosis. Serum MCP-1concentration higher than95.55pg/ml may prompt the patient could have been suffering from tuberculosis (sensitivity:62.5%, specificity:98.7%). And serum MCP-1concentration higher than101.65pg/ml may prompt the patient could have been suffering from spinal tuberculosis (sensitivity:71.1%, specificity:93.7%).Conclusion:(1)Both of the MCP-1-2518-GG genotypeand MCP-1-362-CC genotype were associated with increased serum MCP-1concentrations. And these two genotypes are in synergistic effect on increase serum MCP-1level.(2) The spinal tuberculosis patients'serum MCP-1concentrations are higher than others'. Serum MCP-1concentrations are in a gradually rising trend as the tuberculosis progresses.(3)If serum MCP-1concentration is higher than101.65pg/ml, prompt subjects would have been suffering from spinal tuberculosis. It was first verified the diagnostic value of serum MCP-1concentrations of spinal tuberculosis. This study provid proteomics based on MCP-1in the early diagnosis of sTB.Chapter3The study of the relationship between serum MCP-1concentration and spinal tuberculosis patients' postoperative adverse eventsObjective:To study the relationship between serum MCP-1concentration and spinal tuberculosis patients'postoperative adverse events. Comparison of the sensitivity of MCP-1, ESR and CRP in the diagnosis of postoperative adverse eventMethod:332spinal tuberculosis patients were recruited in our prospective cohort study from December2004to December2010. The follow-up time was more than1year and detailed records of all kinds of complications related to the host immune status were obtained. Detect the serum MCP-1concentration at the3rd,7th,14th day postoperation by ELISA. Analyze the relationship between the serum MCP-1concentration and early postoperative adverse events. Detect the serum MCP-1concentration at the3rd,6th,12th month and each year postoperation by ELISA. Analyze the relationship between the serum MCP-1concentration and mid-term/long-term postoperative adverse events.Results:Serum MCP-1concentrations of patients with early postoperative adverse reactions were lower than patients with good prognosis at7th and14th day (p<0.05). Serum MCP-1concentrations of patients with long-term postoperative adverse reactions were higher than patients with good prognosis at the last follow-up time (p<0.05). When sTB patiens have postoperative adverse events, the serum MCP-1concentration changes earlier. The serum MCP-1changes more significant than the ESR and CRP in the postoperation adverse events during differents times. The serum MCP-1better reflect the. host immune status.Conclusion:When sTB patiens have postoperative adverse events, the serum MCP-1concentration changes more sensitive and has higher specificity of diagnosis. The first research in China to investigate the relationship between serum MCP-1concentrations and postoperative adverse reactions. Serum MCP-1concentrations could be used as a new and more sensitive serological marker for postoperative adverse reactions.