| Objective:To explore the host genetic factors-HLA class Ⅰ antigen presentation pathway genes Low Molecular Weight Proteasome(LMP),Transporter Associated with Antigen Processing(TAP)and Endoplasmic Reticulum Aminopeptidase(ERAP)Single Nucleotide Polymorphisms(SNPs)and the occurrence and development of Tuberculosis(TB)provide a new basis for the treatment and prognosis of tuberculosis.Methods:A total of 449 Han TB patients in Yunnan(including 324 pulmonary tuberculosis and 125 extrapulmonary tuberculosis;278 intreated tuberculosis and 171 retreated tuberculosis)and 435 healthy controls were selected.Use SNaPshot to genotype 24 SNPs of LMP2,LMP7,TAP1,TAP2,ERAP1,and ERAP2 genes,χ2 test analyzes the frequency difference of alleles,genotypes and haplotypes of each SNPs locus in the case and control group.Further stratified analysis,to study the correlation between LMP2,LMP7,TAP1,TAP2,ERAP1 and ERAP2 gene SNPs and tuberculosis in Yunnan Han population.Results:①The alleles and genotype frequencies of the 4 SNPs in the LMP gene were not significantly different between the tuberculosis case group and the control group.Haplotype rs1351383-rs17587-rs2127675-rs2071543:The frequency of C-A-A-G in the TB group was significantly higher than that in the control group(P=5.72×1011,OR=0.040,95%CI:0.010-0.165).②The frequency of the A allele at the rs4155 1 515 locus in the TAP gene was significantly higher in the tuberculosis case group than in the control group(P=8.00×10-4,OR=4.124,95%CI:1.683-10.102),the allele and genotype frequencies of the remaining SNPs were not statistically different between the tuberculosis case group and the control group;Allele TAP1*unknownl(P=4.20×10-5,OR=19.795,95%CI:2.651-147.824)and haplotype TAPI-TAP2:TAP1*unknownl-TAP2*01:02:TGTAGGA-CAC(P=1.06×10-4,OR=17.979,95%CI:2.395-134.980)the frequency in the tuberculosis case group was significantly higher than that in the control group.③The frequency of the G allele at the rs2549782 locus in the ERAP gene was significantly higher in the tuberculosis case group than in the control group(P=0.002.OR=1.348,95%CI:1.117-1.626),and the optimal inheritance mode--dominant inheritance The model showed that the frequency difference between the tuberculosis case group and the control group was statistically significant(P=0.001,OR=1.650,95%CI:1.230-2.220);The frequency of the C allele of rs1056893 in the tuberculosis case group was significantly higher than that in the control group(P=0.002.OR=1.350,95%CI:1.118-1.631),and the optimal inheritance mode—additive inheritance mode showed that the genotype was in The frequency difference between the tuberculosis case group and the control group was statistically significant(P=0.002,OR=1.350,95%CI:1.120-1.630);The allele and genotype frequencies of the remaining SNPs were not statistically different between the tuberculosis case group and the control group;The haplotype constructed by ERAP2 gene locus rs2549782-rs2548538-rs2248374-rs2287988-rs1056893:The frequency of GTAGC in the tuberculosis case group was significantly higher than that in the control group(P=2.40×10-5,OR=1.510,95%CI:1.246-1.829). ④The stratified analysis results showed that the frequency of the A allele of rs41551515 in the tuberculosis group and the retreated tuberculosis group was significantly higher than that of the control group(P=6.90×10-4,OR=4.350,95%CI:1.727-10.954;P=8.77×10-5,OR=5.690,95%CI:2.145-15.095);The dominant inheritance pattern showed that the frequency of rs2549782 genotype between the tuberculosis group and the control group was statistically significant(P=4.00×10-4,OR=1.790.95%CI:1.290-2.480),the G allele of rs2549782 The frequency in the retreatment tuberculosis group was significantly higher than that in the control group(P=4.61×10-5,OR=1.685,95%CI:1.310-2.168),and the optimal inheritance mode-additive inheritance mode analysis showed that the genotype was in the case The difference in frequency between the group and the control group was statistically significant(P<0.0001,OR=1.720,95%CI:1.320-2.230);The frequency of the T allele of rs2548538 in the extrapulmonary tuberculosis group was significantly higher than that in the control group(P=0.001,OR=1.617,95%CI:1.208-2.163),and the frequency in the retreated tuberculosis group was significantly higher than that in the control group(P=9.99×10-5,OR=1.646,95%CI:1.279-2.117),the frequency in the retreated tuberculosis group was significantly higher than that in the initial tuberculosis group(P=0.001,OR=1.623,95%CI:1.234-2.135),the optimal heredity model-additive heredity model analysis showed that the difference in frequency of genotypes between the three groups was statistically significant(P=0.001,OR=1.650,95%CI:1.220-2.220;P=1.00×10-4,OR=1.670.95%CI:1.290-2.170;P=4.00×10-4,OR=1.650.95%CI:1.240-2.190);The frequency of the A allele of rs2248374 in the retreated tuberculosis group was significantly higher than that in the control group(P=4.21×10-4,OR=1.570,95%CI:1.221-2.019),the optimal inheritance mode—additive inheritance mode The analysis showed that the difference in genotype between the two groups was statistically significant(P=0.001,OR=1.570,95%CI:1.220-2.020).The optimal inheritance mode—additive inheritance mode analysis showed that the rs2248374 genotype was in retreatment The frequency difference between the tuberculosis group and the newly-treated tuberculosis group was statistically significant(P=0.002,OR=1.540,95%CI:1.1 60-2.030);The frequency of the G allele of rs2287988 and the C allele of rs1056893 in the retreated tuberculosis group was significantly higher than that in the control group(P=1.33×10-4,OR=1.631,95%CI:1.268-2.098;P=6.55×10-5,OR=1.668,95%CI:1.296-2.145),the optimal heredity model—additive heredity model analysis showed that the difference in frequency between the case group and the control group was statistically significant(P=1.00×10-4,OR=1.660,95%CI:1.280-2.150;P=1.00×10-4,OR=1.660,95%CI:1.290-2.140).Conclusion:This study found the A allele of rs41551515,the G allele of rs2549782,and the C allele of rs 1056893.Allelic TAP1*unknownl,haplotype TAP1*unknown 1-TAP2*0102:TGTAGGA-CAC and rs2549782-rs2548538-rs2248374-rs2287988-rs1056893:G-T-A-G-C may increase the risk of tuberculosis;Haplotypers1351383-rs17587-rs2127675-rs2071543:C-A-A-G may be a protective factor for tuberculosis.The rs2549782,rs2548538,rs2248374,rs2287988,and rs1056893 of the ERAP2 gene may be related to tuberculosis recurrence. |
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