Abstract: 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-α in 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-α in 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.