摘要
目的研究白细胞介素（IL）-1A和IL-1B基因多态性及其与结核易感性之间的关系。方法应用PCR-时间飞行质谱技术（PCR-MassARRAY）分析1032例结核病患者和1008例非结核病患者的IL-1A和IL-1B基因多态性，并通过统计学分析IL-1A和IL-1B各单核苷酸多态性（SNP）位点基因型与活动性结核病之间的关系。结果在筛选出的5个IL-1A和IL-1B标签SNP位点中，rs2853550和rs3783526的等位基因频率在结核组和对照组间存在分布差异（分别为P=0．047和P：0．034）。IL-1BSNPlrs2853550（P=0．025，OR=1．302，95％CI=1．034～1．640，TCvs．CC）具有显著的结核风险，而其他两个IL-1B位点及IL-1A的2个SNP位点则与结核发病无显著关联。在Akaike信息标准（AIC）定义的显性遗传模型下，IL-1BSNPlrs2853550[P=0．019，OR：1．308，95％CI=1．045—1．638，（TC＋TT）vs．CC]位点表现出显著的结核风险。而在隐性遗传模型下发现IL-1ASNP2rs3783526[P=0．040，OR=0．764，95％CI：0．591～0．988，GGVS．（AA＋GA）]位点具有结核抗性，结核风险减少。在IL一1B基因的单体域中，“TG”相比频率最高的“CA”表现出显著的结核风险（P=0．032，OR=1．265，95％CI=1．020～1．567）。IL-1A内单体型中含“GA”的双单体型和IL-1B的单体型中含“TG”的双单体型，1份拷贝时，都表现出显著的结核风险（P=0．014，OR=1．403，95％CI=1．072—1．836；P=0．013，OR=1．339，95％CI=1．063～1．688）。IL-1B的单体型中含“CG”的双单体型，在2份拷贝时，则带有结核抗性（P=0．006，OR=0．664，95％CI=0．494～0．891）。结论IL-1Brs2853550基因多态性可能与结核易感性密切相关，IL-1Ars3783526基因GG基因型可能具有结核抗性。
Objective To study the correlation between genetic polymorphisms of interleukin （IL）-1A/1B and susceptibility to tuberculosis （TB）. Methods Genetic polymorphisms of IL-1A and IL- l B in 1032 TB patients and 1008 non-TB patients were analyzed using PCR-MassARRAY method. The cor- relation between genetic polymorphisms of IL-IA/1B and susceptibility to TB was statistically analyzed. Re- sults Two tag SNPs of IL-1A and three tag SNPs of IL-1B were screened for the study. There were differ- ences in the allele frequencies of rs2853550 and rs3783526 between TB group and non-TB group （P = 0.047 and P=0. 034, respectively）. IL-1B SNP1 rs2853550 （P=0. 025 ,OR= 1. 302,95% CI= 1. 034-1. 640,TC vs. CC） was found to be highly associated with TB, while the other SNPs showed no signifieant correlations with TB. Furthermore, IL-1B SNP1 rs2853550 [ P= 0. 019, OR = 1. 308, 95% CI = 1. 045-1. 638 for （TC＋ TY） vs. CC] in the dominant model conferred significant risk for TB, but IL-1A SNP2 rs3783526 [P= 0. 040, OR = 0. 764,95% CI = 0. 591-0. 988 for GG vs. （AA＋GA） J in the recessive model showed protec- tive effects against TB. The haplotype ＇ TG＇ in the IL-1B block showed a higher risk for TB compared with the common ＇ CA＇ haplotype （ P = 0. 032, OR = 1. 265,95% CI = 1. 020-1. 567 ）. The diplotypes containing＇ GA＇ haplotype in IL-1A block and ＇ TG＇ haplotype in IL-1B block were major risk factors for TB （for one- copy, adjusted P= 0. 014, OR = 1. 403 and 95% CI = 1. 072-1. 836; adjusted P = 0. 013, OR- 1. 339 and 95% CI= 1. 063-1. 688, respectively）, but the diplotype with ＇CG＇ in IL-1B block played a protective effect against TB （for two-copy, P=0. 006, OR=0. 664 and 95% CI=0. 4944）. 891）. Conclusion The genetic polymorphisms of IL-1B rs2853550 might be closely associated with TB, but the GG genotype of IL- 1A SNP rs3783526 might have the characteristic of anti-TB.
出处
《中华微生物学和免疫学杂志》
CAS
CSCD
北大核心
2013年第5期319-325,共7页
Chinese Journal of Microbiology and Immunology
基金
军队医学科技“十二五”重点项目（BWS11J050）
