PD-1、TIM-3和TREM-1基因多态性与肺结核易感性的相关性

Association of PD-1, TIM-3 and TREM.I single nucleotide polymorphisms with pulmonary tuberculosis susceptibility Wang Fengming

目的 探讨细胞程序性死亡因子1（PD-1）、T细胞免疫球蛋白黏蛋白分子3（TIM-3）和髓样细胞触发性受体1（TREM-1）基因多态性与肺结核易感性的相关性.方法 采用病例-对照研究方法,收集2015年3月至2016年9月江苏省常州市金坛区人民医院就诊的100例肺结核患者（肺结核组）和100名社区健康体检者（健康对照组）的外周静脉血.采用高通量测序方法,对66个PD-1、TIM-3和TREM-1基因的单核苷酸多态性（SNP）位点进行基因分型以及连锁不平衡分析和遗传模块分析,探讨两组SNP基因型和等位基因频率的差异.结果 24个SNP被剔除[哈温平衡卡方检验P值（HWE-P）〈0.001或者最小等位基因频率（MAF）〈0.05],剩余42个SNP的基因型频率分布在肺结核组和健康对照组中差异均无统计学意义（均P〉0.05）.PD-1基因的5个 SNP 位点（rs41435650、rs28539662、rs13023138、rs75565781、rs36084323）构成的单体型TACGC在两组之间差异有统计学意义（P=0.014）,其中位点rs28539662与 rs75565781（r2=0.871）及 rs36084323位点（r2=0.864）具有较强的连锁不平衡关系,rs75565781与 rs36084323位点的连锁不平衡关系最强（r2=0.966）.结论 PD-1、TIM-3和TREM-1基因多态性与肺结核的发病无显著相关性.

Objective To investigate the association of programmed cell death 1（PD-1）, T cell immunoglobulin mucin 3（TIM-3）and triggering receptor expressed on myeloid cells-1（TREM-1）genes polymorphisms with pulmonary tuberculosis susceptibility.Methods In this case-control study, peripheral venous blood of 100 pulmonary tuberculosis patients（pulmonary tuberculosis group）in the Jintan People′s Hospital of Changzhou and of community physical examination volunteers（health control group）was collected from Mar 2015 to Sep 2016.A total of 66 single nucleotide polymorphisms（SNP）in PD-1,TIM-3 and TREM1 sequences were selected and SNP genotype and allele frequency were analyzed using the next -generation sequencing technology.Association of these SNP with pulmonary tuberculosis susceptibility was investigated using linkage disequilibrium（LD）analysis and genetic models.Results Among these 66 SNP,24 SNP with Hardy-Weinberg equilibrium P（HWE-P）value 〈0.001 or minimum allele frequency（MAF）〈0.05 were kicked out.The remaining 42 SNP were analyzed with LD analysis and genetic models.There was no significant difference in genotype frequencies between pulmonary tuberculosis group and health control group（all P〉0.05）.Five SNP（rs41435650, rs28539662, rs13023138,rs75565781,rs36084323）in PD-1 were identified in a significant haplotype（TACGC）between pulmonary tuberculosis group and health control group（P=0.014）.Among these haplotypes,strong LD was observed between rs28539662 and rs75565781（r2=0.871）, as well as rs36084323（r2=0.864）.Rs75565781 showed highest correlation with rs 36084323（r2=0.966）.Conclusion These SNP in PD-1, TIM-3 and TREM-1 genes are not associated with the susceptibility of pulmonary tuberculosis.