中国广东地区肺结核HLA-DRB1*040101-44易感基因启动子序列研究

摘要/Abstract

摘要： 目的分析中国广东地区肺结核患者HLA-DR易感基因启动子序列,以期了解HLA与广东地区人群肺结核发病的关联机制,探寻肺结核的发病机理。方法利用核苷酸数据库检索HLADRB1*040101-44易感基因启动子序列,依据启动子区保守序列,设计特异引物对启动子区序列进行PCR扩增,回收特异的PCR产物条带测序,对比结核病组和正常对照组、上述2组分别与网络核苷酸数据库公布的HLA-DR易感基因启动子序列。结果PCR扩增产物测序发现结核病组和对照组DRB1*040101-44启动子区序列一致,但对照组启动子序列与数据库检索序列相比有Y元件盒的变异:-166位的T被A替代,-150位的C被G替代,-137位的T被G替代,-121位的C被G替代,-98位的T被C替代,-73位的A被G替代;在-93到-88位的TATA框、-130到-125位的CAAT框以及-189到-179位的X元件盒中没有碱基变异。结论HLA-DRB1启动子区存在变异,其核酸变异发生在Y元件盒中,但此变异与中国广东地区人群肺结核发病无关联。

关键词: 结核,肺, 启动子, 序列, HLA-DRB

Abstract: Objective To investigate the possible role of HLA in incidence of pulmonary tuberculosis patients in Guangdong in China,we study the promoter structure of HLA susceptive gene DRB1*040101-44. Methods The promoter sequence of HLA susceptive gene DRBl*040101-44 was searched in nucleotide database in NCBI(http://ncbi.nlm.nih.gov/),and according to the conservational nucleotide sequence specific primers was designed to amplify the promoter structure of HLA susceptive gene DRBl*040101-44 by PCR,then the production was reclaimed for PCR direct sequencing;finally the promoter sequences of HLA susceptive gene DRBl*040101-44 in pulmonary tuberculosis patients was compared with normal people and with those sequence published in NCBI. Results The group of pulmonary tuberculosis patients had the same promoter sequences of HLA susceptive gene DRBl*040101-44 as control group.But it was different with those published in nucleotide database in network,and had 6 point mutations in Y component box: T in position-166 was replaced by A,C in-150 by G,T in-137 by G,C in-121 by G,T in-98 by C,A in-73 by G.There were no mutations in nucleotide sites from position-93 to-88 in TATA box,from position-130 to-125 in CAAT box and from position-189 to-179 in X box. Conclusion The promoter structure of HLA susceptive gene DRBl*040101-44 had polymorphism,its nucleotide mutation happened in Y-box,but the polymorphism had no association with development of pulmonary tuberculosis in Guangdong in China.

Key words: Pulmonary tuberculosis, Sequence,promoter, HLA-DRBl

许丽,杨应周,谭卫国,胡志上,吴清芳,张玉华,罗育希,. 中国广东地区肺结核HLA-DRB1*040101-44易感基因启动子序列研究[J]. 中国防痨杂志, 2006, 28(4): 216-220.

Xuli,Yang Yingzhou,Tan Weiguo,et al.. Study on promoter structure of HLA susceptive gene DRB1*040101-44 of Pulmonary Tuberculosis Patients in Guangdong Province in China[J]. Chinese Journal of Antituberculosis, 2006, 28(4): 216-220.

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