本文關鍵詞： 支氣管哮喘 HLA-DQA1基因 干擾素-γ 白介素-4　出處：《瀘州醫(yī)學院》2013年碩士論文　論文類型：學位論文

【摘要】：目的：探討人類白細胞抗原HLA-DQA1基因多態(tài)性與兒童支氣管哮喘的關聯(lián)性，尋找與哮喘發(fā)作有關的易感基因和（或）抑制基因；觀察哮喘組的血清IL-4、IFN-γ水平；比較含有及不含有哮喘相關基因的哮喘患者血清中IL-4、IFN-γ的濃度，分析是否有差異，為進一步研究哮喘發(fā)病機制、預防哮喘發(fā)作及尋找基因水平上治療哮喘的方法提供相應的理論依據(jù)。方法：1.標本采集：哮喘組：選取急性發(fā)作期哮喘患兒共45例為哮喘組。對照組：收集與哮喘組年齡相仿的正常健康兒童60例為對照組。2.檢測方法及指標：采用聚合酶鏈反應—序列特異性引物(PCR-SSP)方法測定哮喘組、對照組的HLA-DQAl等位基因，并計算兩組中各等位基因的基因頻率（直接計算法：基因頻率=陽性基因數(shù)/樣本數(shù)×2），兩組間進行比較；采用雙抗體夾心酶聯(lián)免疫吸附法（ELISA）測定哮喘組、對照組中血清IL-4、IFN-γ水平濃度，并對結果進行統(tǒng)計學處理。3.統(tǒng)計學處理：運用SPPS-17.0軟件系統(tǒng)分析，哮喘組與對照組各等位基因的基因頻率比較采用χ2檢驗，P0.05認為有統(tǒng)計學意義，并計算優(yōu)勢比（OR）及95％置信區(qū)間。測定的血清IL-4、IFN-γ水平濃度，，經SPPS-17.0軟件系統(tǒng)分析后結果用均數(shù)±標準差（±s）表示，兩兩比較采用LSD-t檢驗，相關分析采用Pearson相關性分析，P0.05認為有統(tǒng)計學意義。結果：（1）哮喘組與對照組之間HLA-DQA1等位基因頻率比較：HLA-DQA1*0301在哮喘組的基因頻率（20.00%）明顯高于對照組（8.33%），χ2=7.159，P=0.007，有統(tǒng)計學意義，OR為3.333（95%置信區(qū)間為1.35-8.229）。HLA-DQA1*0104在哮喘組的基因頻率（27.77%）明顯低于對照組（38.33%），χ2值為5.234，P=0.022，差異有統(tǒng)計學意義，OR為0.380，95%置信區(qū)間為（0.164-0.880）。（2）哮喘組和對照組外周血IL-4、INF-γ水平比較：哮喘組中血清IL-4水平(116.45±20.45)明顯高于對照組(90.34±13.43),差異有統(tǒng)計學意義（P0.05）；哮喘組血清IFN-γ水平(65.34±12.34)明顯低于對照組(84.23±13.42)，差異有統(tǒng)計學意義（P0.05）；（3）哮喘組IFN-γ與IL-4的相關性分析：哮喘急性發(fā)作期血清IFN-γ與IL-4水平呈負相關（r=-0.356，P0.05）。（4）HLA-DQA1*0301陽性哮喘患者（18例）與HLA-DQA1*0301陰性哮喘患者（27例）IFN-γ（水平分別為67.12±13.24、69.13±12.16）、IL-4（水平分別為114.23±23.45、113.21±20.34）比較，差異無統(tǒng)計學意義（P0.05）。結論：1.HLA-DQA1*0301基因可能為兒童支氣管哮喘的易感基因；HLA-DQA1*0104基因可能為兒童哮喘的免疫抑制基因。2.哮喘組中IFN-γ較對照組明顯下降，IL-4則明顯升高，哮喘組中兩者呈負相關，表明Th1/Th2免疫失衡仍可能是哮喘發(fā)作的重要因素。3.存在與不存在易感基因的哮喘患者血清IFN-γ、IL-4水平比較無顯著差異，表明HLA-DQA1*0301可能僅某種特應性變應原所致的哮喘有關，亦表明哮喘發(fā)作與否不是由某個等位基因決定，其發(fā)作可能為多基因共同作用的結果。
[Abstract]:Objective: to investigate the association between polymorphisms of human leukocyte antigen (HLA-DQA1) gene and bronchial asthma in children, and to search for susceptibility genes and / or suppressor genes related to asthma attack. The levels of IL-4 and IFN- 緯 in serum of asthmatic group were observed. To compare the levels of IL-4 and IFN- 緯 in the serum of asthmatic patients with and without asthmatic related genes, and to analyze whether there are differences in the levels of IL-4 and IFN- 緯, so as to further study the pathogenesis of asthma. Methods 1. Specimen collection: asthma group: 45 children with acute asthma were selected as asthma group. 60 healthy children of the same age as asthma group were collected as control group. 2. Detection methods and indicators: polymerase chain reaction-sequence specific primers (PCR) were used. The asthma group was determined by PCR-SSP. The HLA-DQAl allele of the control group and the gene frequency of each allele in the two groups were calculated (direct calculation method: gene frequency = number of positive gene / sample number 脳 2G), the comparison was made between the two groups. The serum levels of IL-4 and IFN- 緯 in asthma group and control group were determined by double antibody sandwich enzyme linked immunosorbent assay (Elisa). Statistical analysis: using SPPS-17.0 software, the allele frequencies of asthma group and control group were compared by 蠂 2 test. P0.05 thought there was statistical significance, and calculated the odds ratio (OR) and 95% confidence interval. The serum IL-4 level of IFN- 緯 was measured. The results were expressed as mean 鹵standard deviation (鹵s) after systematic analysis by SPPS-17.0 software. LSD-t test was used for pairwise comparison and Pearson correlation analysis was used for correlation analysis. Results the allele frequency of HLA-DQA1 between the asthma group and the control group was higher than that of the control group (P < 0.05). (20.00) was significantly higher than the control group (8.33). 蠂 2 = 7.159%, P = 0.007, with statistical significance. The OR was 3.333 / 95% CI = 1.35-8.229.HLA-DQA1 / 0104 gene frequency in asthma group was significantly lower than that in control group (P < 0.05). 38.33). 蠂 ~ 2 value was 5.234 (P = 0.022), the difference was statistically significant (OR = 0.380). The 95% confidence interval was 0.164-0.880) IL-4 in peripheral blood of asthmatic group and control group. Comparison of INF- 緯 levels: serum IL-4 levels in asthma group were significantly higher than those in control group (116.45 鹵20.45) and 90.34 鹵13.43). The difference was statistically significant (P 0.05). The level of IFN- 緯 in asthmatic group (65.34 鹵12.34) was significantly lower than that in control group (84.23 鹵13.42), and the difference was statistically significant (P 0.05). (3) correlation analysis between IFN- 緯 and IL-4 in asthma group: serum IFN- 緯 and IL-4 level were negatively correlated with IL-4 in acute episode of asthma. There were 18 patients with HLA-DQA1-0301 positive asthma and 27 patients with HLA-DQA1*0301 negative asthma. The levels were 67.12 鹵13.24 respectively. Comparison of IL-4 levels (114.23 鹵23.45, 113.21 鹵20.34). Conclusion: 1. HLA-DQA1 / 0301 gene may be a susceptible gene for bronchial asthma in children. HLA-DQA1*0104 gene may be the immunosuppressive gene of childhood asthma. IFN- 緯 in asthma group was significantly lower than that in control group and IL-4 was significantly increased. There was a negative correlation between the two in asthma group, indicating that Th1/Th2 immune imbalance may still be an important factor of asthma attack. 3. The presence and absence of susceptibility gene in the serum IFN- 緯 of asthma patients. There was no significant difference in IL-4 levels, suggesting that HLA-DQA1*0301 might be related only to asthma caused by an atopic allergen, and that asthma attack was not determined by an allele. The attack may be the result of multiple gene interaction.
【學位授予單位】：瀘州醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R725.6

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