中文摘要：

目的 对比分析飞行时间质谱技术（MALDI-TOF）和TaqMan探针筛选与结核病易感性相关单核苷酸多态性（SNP）位点的结果,以及联合应用的方法学和效果评价.方法 选取2010年10月至2011年4月在深圳市第三人民医院收治并确诊的结核病患者400例为结核病组,对照组为同时期收集的健康体检者300名,利用MALDI-TOF对选取的7个SNP位点（rs2227476、rs1800795、rs56077270、rs1800797、rs2227484、rs2227472和rs2227473）同时进行基因分型,初步筛选易感SNP位点;与结核病易感相关的单个SNP位点,采用基于TaqMan探针技术的实时荧光定量PCR对同样的标本再进行基因分型,比较两种方法的准确性与敏感度;以rs2227473位点为实例对分型结果的基因频率进行分析,确定肺结核的易感SNP.结果 MALDI-TOF分型成功率为99.7％（698/700）,TaqMan探针技术为98.4％（689/700）;在基因分型过程中,MALDI-TOF与TaqMan探针方法对1例标本的分型结果不一致,经过对此分型结果进行了测序验证,MALDI-TOF的分型结果正确,MALDI-TOF在准确性和敏感度比TaqMan法稍高.位点rs2227473基因频率分析中,结核病组G等位基因频率（90.3％,722/800）明显高于对照组（82.5％,495/600）（x2=6.911,P=0.009）.结论 上述肺结核易感基因的筛选方法是可行的;实例分析中,将两种方法联合应用,发现了IL-22基因rs2227473位点等位基因G可能与肺结核发病相关,两位点中等位基因A可能为保护性基因.

英文摘要：

Objective To develop a new method based on MALDI-TOF and TaqMan probe for screening the single nucleotide polymorphisms （SNP） with susceptibility to tuberculosis and evaluate its clinical application value.Methods At first,total 7 sites we targeted were detected by MALDI-TOF simultaneously.The single SNP site was detected by using TaqMan probe technology.The two methods were compared by accuracy and sensitivity.We determined a susceptibility gene site by comparing genotype and gene frequency between 400 TB patients and 300 healthy controls by using this method.Results The success rate of genotyping by MALDI-TOF was 99.7％ （698/700）,that of TaqMan probe technology was 98.4％ （689/700）.The frequency of G allele at rs2227473 in patient groups （90.3％,722/800） was significantly higher than that in control groups （82.5％,495/600） （x2=6.911,P =0.009）.The other 6 SNP sites had no significant difference between two groups.Conclusion We successfully established a new method for screening the SNPs with susceptibility to tuberculosis.The polymorphism of IL22 rs2227473 allele G may be associated with the susceptibility to pulmonary tuberculosis,allele A may be the protective gene.