HLAⅡ基因多态性与肺炎支原体肺炎的易感性分析

Association between HLAⅡgene polymorphism and genetic susceptibility to Mycoplasma pneumoniae pneumonia

目的：探讨肺炎支原体肺炎（ MPP）患儿与人类白细胞抗原（ HLA）Ⅱ类（ HLA-DQA1、HLA-DRB1）等位基因的相关性及连锁不平衡,寻找与MPP发病有关的易感基因/或保护基因,进一步研究MPP发病机制,从而为从基因水平治疗MPP的方法提供理论依据。方法利用序列特异性聚合酶链反应（ SSP-PCR）对本院60例确诊的MPP患儿和30例健康儿童进行HLA-DQA1、HLA-DRB1等位基因以及有关基因亚型分析,比较组间基因频率、单倍型频率、连锁不平衡及疾病相关性分析。结果 MPP患儿 HLA-DQA1＊0201/＊0301的频率分别增高到35.83%/30.00%,与正常儿童的16.67%/8.33%的频率相比,差异具有统计学意义（χ2=12.139,P〈0.05,OR=5.059；χ2=15.142,P〈0.05,OR=7.500）；MPP患儿HLA-DQA1＊0401的频率为12.50%,与正常儿童的40.00%的频率相比,差异具有统计学意义（χ2=24.638,P〈0.05,OR=0.083）；MPP患儿HLA-DRB1＊07/＊15的频率分别增高到38.33%/30.00%,与正常儿童的20.00%/16.67%的频率相比,差异具有统计学意义（χ2=11.735,P〈0.05,OR=4.929；χ2=5.692,P〈0.05,OR=3.000）；MPP患儿HLA-DRB1＊11的频率为15.00%,与正常儿童的43.33%的频率相比,差异具有统计学意义（χ2=19.448, P〈0.05, OR=0.087）。结论 HLA-DQA1＊0201/＊0301基因可能是儿童MPP患儿的易感因素；HLA-DQA1＊0401可能对儿童MPP的发病具有保护作用；HLA-DRB1＊07/＊15基因可能是 MPP 患儿的易感因素, HLA-DRB1＊11可能对儿童MPP的发病具有保护作用。 HLA-DQA1与HLA-DRB1等位基因之间不存在广泛的连锁不平衡。

Objective To investigate the correlations between HLAⅡgene polymorphism and the development of Mycoplasma pneumoniae pneumonia （ MPP ） in children and to identify the susceptibility genes and protective genes for MPP for further elucidating the pathogenesis of MPP and providing the guid-ance for researches on gene therapy for MPP. Methods Genotypes of HLAⅡgene （ HLA-DQA1 and HLA-DRB1） in 60 children with MPP and 30 healthy children were detected by using sequence specific primer polymerase chain reaction （ SSP-PCR） . The haplotype frequencies, linkage disequilibrium and correlations with MPP were analyzed by using Arlequin software and Chi-square test. Results The frequencies of HLA-DQA1＊0201/＊0301 in children with MPP （35. 83%/30. 00%） were higher than those in healthy children （16. 67%/8. 33%） （χ2=12. 139, P〈0. 05, OR=5. 059;χ2=15. 142, P〈0. 05, OR=7. 500）. However, the frequency of HLA-DQA1＊0401 in children with MPP decreased to 12. 50% as compared with 40. 00%in healthy children （χ2=24. 638, P〈0. 05, OR=0. 083）. The frequencies of HLA-DRB1＊07/＊15 in children with MPP increased to 38. 33%/30. 00% as compared with 20. 00%/16. 67% in healthy childrennbsp;（χ2=11. 735, P〈0. 05, OR=4. 929; χ2=5. 692, P〈0. 05, OR=3. 000）. But the frequency of HLA-DRB1＊11 dropped to 15. 00% as compared with 43. 33% in healthy children （χ2=19. 448, P〈0. 05, OR=0. 087）. Conclusion HLA-DQA1＊0201, HLA-DQA1＊0301, HLA-DRB1＊07 and HLA-DRB1＊15 might be the susceptibility genes for MPP in children, while HLA-DQA1＊0401 and HLA-DRB1＊11 were probably associated with the resistance to MPP. No extensive linkage disequilibrium was found between HLA-DQA1 and HLA-DRB1.