关键词: 结核, 肺, 多态性, 单核苷酸, 白细胞介素类, 光谱法, 质量, 基质辅助激光解吸电离, DNA探针, 疾病遗传易感性

Abstract: 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) (χ²=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 IL-22 rs2227473 allele G may be associated with the susceptibility to pulmonary tuberculosis, allele A may be the protective gene.

Key words: Tuberculosis, pulmonary, Polymorphism, single nucleotide, Interleukins, Spectrometry, mass, matrix-assisted laser desorption-ionization, DNA probes, Genetic predisposition to disease