ERAP1和ERAP2基因多态性与肺结核遗传易感性的关联

Association of ERAP1 and ERAP2 gene polymorphisms with genetic susceptibility to pulmonary tuberculosis

目的探讨内质网氨肽酶1/2(ERAP1/2)基因多态性与肺结核患者遗传易感性的关联。方法选取温州医科大学附属衢州医院2020年3月-2021年3月302例肺结核感染患者纳入结核组,另选取300名健康体检者纳入对照组,采用SNaPshot分型技术检测纳入对象ERAP1、ERAP2基因位点基因分型,比较结核组与对照组基因型频率,通过Logistic回归分析ERAP1、ERAP2单核苷酸多态性与肺结核感染发生的关系。结果结核组ERAP1基因rs27044位点、rs26618位点CC基因型比例高于对照组,ERAP2基因rs2549782位点TT基因型比例低于对照组(P<0.05);结核组ERAP1基因rs27044位点、rs26618位点C基因频率高于对照组,ERAP2基因rs2549782位点T基因频率低于对照组(P<0.05);Logistic回归分析结果显示体质量指数、肺结核患者接触史、ERAP1基因rs27044位点CC基因型、rs26618位点CC基因型是肺结核发生的影响因素(P<0.05),卡介苗接种史、ERAP2基因rs2549782位点TT基因型是肺结核的保护因素;ERAP1-rs27044位点CC基因型肺结核患者血清白细胞介素-1(IL-1)、IL-6、肿瘤坏死因子-α(TNF-α)高于CG或GG基因型,ERAP1-rs26618位点CC基因型患者血清IL-1、IL-6、TNF-α高于CT或TT基因型,ERAP2-rs2549782位点TT基因型患者血清IL-1、IL-6、TNF-α低于TG或GG基因型(P<0.05)。结论ERAP1基因rs27044位点CC基因型、rs26618位点CC基因型是肺结核易感的危险基因型,ERAP2基因rs2549782位点TT基因型是肺结核不易感的保护基因型。

OBJECTIVE To investigate the association of endoplasmic reticulum aminopeptidase 1/2(ERAP1/ERAP2)gene polymorphisms with genetic susceptibility in patients with pulmonary tuberculosis infection.METHODS A total of 302 patients with tuberculosis between Mar.2020 and Mar.2021 in Quzhou Hospital Affiliated to Wenzhou Medical University were selected to be included in the tuberculosis group,and another 300 healthy people underwent physical examination were selected to be included in the control group.The genotypes of ERAP1 and ERAP2 gene loci in the included subjects were detected by SNaPshot genotyping technique.The frequencies of different genotypes were compared between tuberculosis group and control group.The relationship between single nucleotide polymorphisms(SNP)of ERAP1 and ERAP2 and the occurrence of pulmonary tuberculosis infection was analyzed by Logistic regression analysis.RESULTS The proportion of CC genotype at locus rs27044 and rs26618 of ERAP1 gene in the tuberculosis group was higher than that in the control group,while proportion of TT genotype at locus rs2549782 of ERAP2 gene was lower than that in the control group(P<0.05).The frequency of C gene at locus rs27044 and rs26618 of ERAP1 gene in the tuberculosis group was higher than that in the control group,while frequency of T gene at locus rs2549782 of ERAP2 gene was lower than that in the control group(P<0.05).The results of Logistic regression analysis showed that BMI,history of exposure to tuberculosis patients,CC genotype at locus rs27044 of ERAP1 gene,and CC genotype at locus rs26618 were influential factors for the occurrence of tuberculosis,while history of BCG vaccination and TT genotype at locus rs2549782 of ERAP2 gene were protective factors for less susceptibility to TB.The levels of serum IL-1,IL-6 and TNF-αin patients with CC genotype at locus rs27044 of ERAP1 gene were higher than those with CG or GG genotype,and those in patients with CC genotype at locus rs26618 of ERAP1 gene were higher those in patients with than CT or TT genotype.The levels of serum IL-1,IL-6 and TNF-αin patients with TT genotype at locus rs2549782 of ERAP2 gene were lower than those with TG or GG genotype(P<0.05).CONCLUSION CC genotype at locus rs27044 and locus rs26618 of ERAP1 gene were risk genotypes for tuberculosis susceptibility,while TT genotype at locus rs2549782 of ERAP2 gene was a protective genotype for TB non-susceptibility.