刘楠楠,刘舒媛,王辉,张新文,李传印,史荔,张淑琼
LIU Nannan,LIU Shuyuan,WANG Hui,ZHANG Xinwen,LI Chuanyin,SHI Li,ZHANG Shuqiong

• 1:中国医学科学院&北京协和医学院医学生物学研究所&云南省重大传染病疫苗研发重点实验室
• 2:昆明市第三人民医院

摘要(Abstract)：

目的:研究云南省汉族人群LMP2、LMP7基因单核苷酸多态性(SNP)与结核病(TB)的相关性。方法:选取449例云南省汉族TB患者(其中肺TB 324例、肺外TB 125例)作为病例组,367例健康人群作为对照组;采用SNa Pshot分型法对LMP2基因的3个SNP位点rs1351383(T> G)、rs17587(C> T)、rs2127675(A> G)和LMP7基因的rs2071543(G> T)位点进行基因分型,比较这4个SNP位点等位基因和基因型在病例组和对照组中的频率,结合遗传模式分析和单倍型分析,研究LMP2和LMP7基因SNP多态性与TB的相关性。结果:经Bonferroni校正后,4个SNP位点的等位基因及基因型频率在病例组和对照组中差异均无统计学意义(P>0. 012 5);但在分层研究中,rs1351383位点的C等位基因在肺外TB患者中的频率显著高于对照组(P=0. 010,OR=1. 377,95%CI为1. 030～1. 841),加性遗传模式分析显示该位点基因型在病例组和对照组间频率的差异具有统计学意义(P=0. 008,OR=1. 520,95%CI为1. 120～2. 080); rs1351383-rs17587-rs2127675-rs2071543单倍型C-G-G-G在肺外TB患者中的频率显著高于对照组(P=0. 003,OR=1. 982,95%CI为1. 246～3. 154)。结论:云南省汉族人群中LMP基因的多态位点rs1351383的C等位基因及其rs1351383-rs17587-rs2127675-rs2071543单倍型C-G-G-G可能增加肺外TB的患病风险。
Objective: To investigate the association between LMP2 and LMP7 gene single nucleotide polymorphisms( SNPs) and Tuberculosis( TB) of Han population in Yunnan. Methods: A total of449 patients with TB( including 324 cases with pulmonary TB and 125 cases with extrapulmonary TB)and 367 healthy individuals of the Han people in Yunnan province were recruited in this study.SNaPshot genotyping was used to genotype the three SNPs of the LMP2 genes: rs1351383( T > G),rs17587( C > T),rs2127675( A > G),and rs2071543( G > T) of the LMP7 genes. The allelic and genotypic frequencies of the four SNPs in TB cases and the control group were compared using different inheritance models. Furthermore, the haplotype were constructed and analyzed. Results: After Bonferroni correction there was no difference between TB cases and the control group( P > 0. 0125) in the allelic and genotypic frequencies of the four SNPs. However,the stratified study showed that the frequency of the C allele of rs1351383 in the group with extrapulmonary TB was significantly higher than that of the control group( P = 0. 010,OR = 1. 377,95% CI: 1. 030 ～ 1. 841),while the genotype difference was showed between the EPTB and TB cases in the analysis of additive genetic model( P =0. 008,OR = 1. 520,95% CI: 1. 120 ～ 2. 080). The frequency of haplotype rs1351383-rs17587-rs2127675-rs2071543: C-G-G-G was significantly higher in the group with extrapulmonary TB( P =0. 015,OR = 1. 982,95% CI: 1. 246 ～ 3. 154,after B. correction) than that in the control group.Conclusion: rs1351383-C in LMP2 gene, as well as haplotype rs1351383-rs17587-rs2127675-rs2071543: C-G-G-G may increase the susceptibility of extrapulmonary TB in Yunnan Han population.

关键词(KeyWords)： 多态性,单核苷酸;低相对分子量蛋白酶体基因;结核病;云南汉族
polymorphism,single nucleotide(SNP);low molecular weight proteasome(LMP) gene;tuberculosis(TB);han population of yunnan

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(31401063);; 中国医学科学院医学与健康科技创新工程重大协同创新项目(2016-I2M-2-001)

作者(Author): 刘楠楠,刘舒媛,王辉,张新文,李传印,史荔,张淑琼
LIU Nannan,LIU Shuyuan,WANG Hui,ZHANG Xinwen,LI Chuanyin,SHI Li,ZHANG Shuqiong

DOI: 10.19367/j.cnki.2096-8388.2020.05.003

参考文献(References)：

• [1]FURIN J,COX H,PAI M. Tuberculosis[J]. The Lancet,2019,393(10181):1642-1656.
• [2]SCHURR E. Is susceptibility to tuberculosis acquired or inherited[J]. Journal of Internal Medicine,2007,261(2):106-111.
• [3] ABEL L,EL-BAGHDADI J,BOUSFIHA A A,et al.Human genetics of tuberculosis:A long and winding road[J]. Philos Trans R Soc Lond B Biol Sci,2014,369(1645):20130428.
• [4]李彤，刘城秀，姚宇峰，等．云南汉族人群LMP基因多态性与丙型肝炎病毒慢性感染的相关性[J]．中华医学遗传学杂志，2016,33(6):806-810.
• [5]刘舒媛，李传印，李盈甫，等．LMP2基因多态性与云南汉族人群非小细胞肺癌的发生发展的相关性[J]．贵州医科大学学报，2017,42(1):15-20.
• [6]NEEFJES J,JONGSMA M L M,PAUL P,et al. Towards a systems understanding of MHC class I and MHC class II antigen presentation[J]. Nature Reviews Immunology,2011,11(12):823-836.
• [7]HUANG P,DONG L,LU X M,et al. Genetic variants in antigen presentation-related genes influence susceptibility to hepatitis C virus and viral clearance:A case control study[J]. BMC Infectious Diseases,2014,14(1):716.
• [8]ZANG F,YAO Y N,LIU M,et al. The association of LMP7 and TAP2 gene polymorphisms with treatment response to interferon/ribavirin in patients with genotype 1chronic hepatitis C[J]. Int J Mol Med,2017,40(6):1983-1990.
• [9]HAROON N,MAKSYMOWYCH W P,RAHMAN P,et al. Radiographic severity of ankylosing spondylitis is associated with polymorphism of the large multifunctional peptidase 2 gene in the Spondyloarthritis Research Consortium of Canada cohort[J]. Arthritis&Rheumatism,2012,64(4):1119-1126.
• [10]MA X,YANG C,TANG R,et al. Association between LMP2 and LMP7 gene polymorphisms and the risk of gastric cancer:A case-control study[J]. Oncology Letters,2015,10(1):509-517.
• [11]WU Y,LIU D F,ZHANG J J,et al. Association between LMP2/LMP7 genetic variability and cancer susceptibility,especially among Asians:evidence from a metaanalysis[J]. Oncotarget, 2017, 8(37):62445-62453.
• [12]SONG L,MA N N,HAN L,et al. Association between LMP2/LMP7 genetic variability and the metastasis risk of ovarian cancer in Chinese women in Beijing[J]. Human Immunology,2014,75(3):239-244.
• [13]MANDAL R K,DAR S A,JAWED A,et al. Impact of LMP7(rs2071543)gene polymorphism in increasing cancer risk:evidence from a meta-analysis and trial sequential analysis[J]. Oncotarget,2018,9(5):6572-6585.
• [14]SHI Y Y,HE L. SHEsis,a powerful software platform for analyses of linkage disequilibrium, haplotype construction,and genetic association at polymorphism loci[J]. Cell Res,2005,15(2):97-98.
• [15]SOLE X,GUINO E,VALLS J,et al. SNPStats:a web tool for the analysis of association studies[J]. Bioinformatics,2006,22(15):1928-1929.
• [16]王丹妹，莫燕娜，吉丽敏，等．LMP基因多态性与疾病相关性的研究现状[J]．中华全科医学，2010(8):1033-1035.
• [17]VAN KAER L,ASHTON-RICKARDT P G,EICHELBERGER M,et al. Altered peptidase and viral-specific T cell response in LMP2 mutant mice[J]. Immunity,1994,1(7):533-541.
• [18]YORK I A,ROCK K L. Antigen processing and presentation by the class i major histocompatibility complex[J].Annual Review of Immunology,1996,14(1):369-396.
• [19]LV Y,YAN B,YANG H L,et al. LMP2/LMP7 gene variant:A risk factor for intestinal Mycobacterium tuberculosis infection in the Chinese population[J]. Journal of Gastroenterology and Hepatology,2011,26(7):1145-1150.
• [20]QIAN J,LIU H L,WEI S,et al. Association between putative functional variants in the PSMB9 gene and risk of melanoma-re-analysis of published melanoma genomewide association studies[J]. Pigment Cell&Melanoma Research,2013,26(3):392-401.
• [21]WANG D M,ZHOU Y,JI L M,et al. Association of LMP/TAP gene polymorphisms with tuberculosis susceptibility in Li population in China[J]. PLo S One,2012,7(3):e33051.

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