HLA-A、HLA-B、HLA-DRB1等位基因多态性与中国北方汉族肺癌患者遗传易感相关性的研究
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摘要
目的:探讨中国北方汉族人群中HLA-A、HLA-B、HLA-DRB1等位基因多态性与肺癌遗传易感性之间的关系。
方法:采用盐酸胍法提取DNA,直接测序分型(SBT)结合序列特异性引物聚合酶链反应技术(PCR-SSP)对无血缘关系的籍贯为中国北方民族为汉族的140名肺癌患者及483名健康志愿者的HLA-A、HLA-B、HLA-DRB1等位基因多态性进行检测。应用arlequin软件(ver2.000)进行等位基因频率的计算、连锁不平衡分析,各个等位基因在人群中的差异用SPSS软件(ver13.0)进行卡方检验,对P值<0.05的计算OR值和95%可信区间。
结果:采用高分技术HLA-A查出等位基因32个,HLA-B查出等位基因66个,HLA-DRB1查出等位基因44个。其中:HLA-A*26:01、HLA-B*15:18、HLA-B*38:02、HLA-DRB1*04:01、HLA-DRB1*04:02、HLA-DRB1*12:01,在肺癌病人中频率高于正常对照,P值分别为:0.021、0.001、0.015、0.021、0.010、0.046,OR值分别为:3.513、3.842、2.715、3.512、13.986、1.828;HLA-DRB1*10:01和HLA-DRB1*13:02在肺癌病人中频率低于正常对照,P值分别为:0.017和0.014,OR值分别为0.135和0.122。单倍型HLA-A*02:07-B*46:01-DRB1*09:01和HLA-A*02:06-B*51:01在肺癌病人中频率高于正常对照,P值分别为0.034和0.006,OR值分别为2.348和3.969;HLA-A*11:01-DRB1*15:01在肺癌病人中频率低于正常对照,P值为0.026,OR=0.146;另外单倍型HLA-A*01:01-B*37:01在正常对照中频率为0.02070但在肺癌病人中未检出。
结论:在中国北方汉族人群中HLA-A*26:01、HLA-B*15:18、HLA-B*38:02、HLA-DRB1*04:01、HLA-DRB1*04:02、HLA-DRB1*12:01以及单倍型HLA-A*02:07-B*46:01-DRB1*09:01和HLA-A*02:06-B*51:01和肺癌的发病可能存在正相关关系, HLA-DRB1*10:01和HLA-DRB1*13:02以及单倍型HLA-A*11:01-DRB1*15:01和肺癌的发病可能存在负相关关系。
Objective: To investigate differences of HLA-A, B and DRB1 alleles among lung carcinoma patients and healthy controls, in order to determine the correlation between genetic susceptibility to lung carcinoma of Han nationality from North China and the polymorphisms of HLA-A,B and DRB1.
Methods: The polymorphisms of HLA-A, B and DRB1 alleles in 140 unrelated patients with lung carcinoma and 483 unrelated normal controls of Han nationality from North China were examined using sequence-based typing(SBT)and polymerase chain reaction with sequence-specific primer(PCR-SSP).
Results: The frequencies of HLA-A*26:01, HLA-B*15:18, HLA-B*38:02, HLA-DRB1*04:01, HLA-DRB1*04:02 and HLA-DRB1*12:01 were higher in the lung carcinoma group than those in the normal control group, with P values were respectively 0.021,0.001,0.015,0.021,0.010 and 0.046, while OR values were respectively 3.513,3.842,2.715,3.512,13.986 and 1.828. The frequencies of HLA-DRB1*10:01 and HLA-DRB1*13:02 were lower in the lung carcinoma group than those in the normal control group, with P values were respectively 0.017 and 0.014, while OR values were respectively 0.135 and 0.122. The frequencies of haplotype HLA-A*02:07-B*46:01-DRB1*09:01 and HLA-A*02:06-B*51:01 were higher in the lung carcinoma group than those in the normal control group, with P values were respectively 0.034 and 0.006, while OR values were respectively 2.348 and 3.969. The frequency of haplotype HLA-A*11:01-DRB1*15:01 was lower in the lung carcinoma group than those in the normal control group, with P value was 0.026 and OR was 0.146. The frequency of haplotype HLA-A*01:01-B*37:01 was 0.02070 but not found in lung carcinoma group.
Conclusion: The frequencies of some HLA alleles(HLA-A*26:01, HLA-B*15:18, HLA-B*38:02, HLA-DRB1*04:01, HLA-DRB1*04:02, HLA-DRB1*12:01, HLA-DRB1*10:01 and HLA-DRB1*13:02 ) and haplotypes( HLA-A*02:07-B*46:01-DRB1*09:01, HLA-A*02:06-B*51:01 and HLA-A*11:01-DRB1*15:01)maybe related with the susceptibility to lung carcinoma of Han nationality from North China.
方法:采用盐酸胍法提取DNA,直接测序分型(SBT)结合序列特异性引物聚合酶链反应技术(PCR-SSP)对无血缘关系的籍贯为中国北方民族为汉族的140名肺癌患者及483名健康志愿者的HLA-A、HLA-B、HLA-DRB1等位基因多态性进行检测。应用arlequin软件(ver2.000)进行等位基因频率的计算、连锁不平衡分析,各个等位基因在人群中的差异用SPSS软件(ver13.0)进行卡方检验,对P值<0.05的计算OR值和95%可信区间。
结果:采用高分技术HLA-A查出等位基因32个,HLA-B查出等位基因66个,HLA-DRB1查出等位基因44个。其中:HLA-A*26:01、HLA-B*15:18、HLA-B*38:02、HLA-DRB1*04:01、HLA-DRB1*04:02、HLA-DRB1*12:01,在肺癌病人中频率高于正常对照,P值分别为:0.021、0.001、0.015、0.021、0.010、0.046,OR值分别为:3.513、3.842、2.715、3.512、13.986、1.828;HLA-DRB1*10:01和HLA-DRB1*13:02在肺癌病人中频率低于正常对照,P值分别为:0.017和0.014,OR值分别为0.135和0.122。单倍型HLA-A*02:07-B*46:01-DRB1*09:01和HLA-A*02:06-B*51:01在肺癌病人中频率高于正常对照,P值分别为0.034和0.006,OR值分别为2.348和3.969;HLA-A*11:01-DRB1*15:01在肺癌病人中频率低于正常对照,P值为0.026,OR=0.146;另外单倍型HLA-A*01:01-B*37:01在正常对照中频率为0.02070但在肺癌病人中未检出。
结论:在中国北方汉族人群中HLA-A*26:01、HLA-B*15:18、HLA-B*38:02、HLA-DRB1*04:01、HLA-DRB1*04:02、HLA-DRB1*12:01以及单倍型HLA-A*02:07-B*46:01-DRB1*09:01和HLA-A*02:06-B*51:01和肺癌的发病可能存在正相关关系, HLA-DRB1*10:01和HLA-DRB1*13:02以及单倍型HLA-A*11:01-DRB1*15:01和肺癌的发病可能存在负相关关系。
Objective: To investigate differences of HLA-A, B and DRB1 alleles among lung carcinoma patients and healthy controls, in order to determine the correlation between genetic susceptibility to lung carcinoma of Han nationality from North China and the polymorphisms of HLA-A,B and DRB1.
Methods: The polymorphisms of HLA-A, B and DRB1 alleles in 140 unrelated patients with lung carcinoma and 483 unrelated normal controls of Han nationality from North China were examined using sequence-based typing(SBT)and polymerase chain reaction with sequence-specific primer(PCR-SSP).
Results: The frequencies of HLA-A*26:01, HLA-B*15:18, HLA-B*38:02, HLA-DRB1*04:01, HLA-DRB1*04:02 and HLA-DRB1*12:01 were higher in the lung carcinoma group than those in the normal control group, with P values were respectively 0.021,0.001,0.015,0.021,0.010 and 0.046, while OR values were respectively 3.513,3.842,2.715,3.512,13.986 and 1.828. The frequencies of HLA-DRB1*10:01 and HLA-DRB1*13:02 were lower in the lung carcinoma group than those in the normal control group, with P values were respectively 0.017 and 0.014, while OR values were respectively 0.135 and 0.122. The frequencies of haplotype HLA-A*02:07-B*46:01-DRB1*09:01 and HLA-A*02:06-B*51:01 were higher in the lung carcinoma group than those in the normal control group, with P values were respectively 0.034 and 0.006, while OR values were respectively 2.348 and 3.969. The frequency of haplotype HLA-A*11:01-DRB1*15:01 was lower in the lung carcinoma group than those in the normal control group, with P value was 0.026 and OR was 0.146. The frequency of haplotype HLA-A*01:01-B*37:01 was 0.02070 but not found in lung carcinoma group.
Conclusion: The frequencies of some HLA alleles(HLA-A*26:01, HLA-B*15:18, HLA-B*38:02, HLA-DRB1*04:01, HLA-DRB1*04:02, HLA-DRB1*12:01, HLA-DRB1*10:01 and HLA-DRB1*13:02 ) and haplotypes( HLA-A*02:07-B*46:01-DRB1*09:01, HLA-A*02:06-B*51:01 and HLA-A*11:01-DRB1*15:01)maybe related with the susceptibility to lung carcinoma of Han nationality from North China.
引文
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