白介素-10基因多态性与结核病易感性的病例对照家系研究
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摘要
目的探讨IL-10基因-1082G/A的基因多态性与肺结核易感性的关系。方法通过家系病例对照设计,用聚合酶联反应-限制性片段长度多态性检测IL-10基因rs1800896位点,分析基因型和等位基因的频率在病例家系人群和对照家系人群及其一级亲属中的分布差异;采用logistic回归模型进行所研究基因的遗传变异与结核病发病风险的关联性分析。结果 180例样本中病例家系组有28组,共89人,患病人数为41人,一级亲属患病23人;对照家系组有35组,共91人。对于IL-10基因rs1800896位点,与A等位基因携带者相比,携带G等位基因的个体结核病发病风险显著增高(OR=4.48,95%CI=1.14-17.61)。结论 IL-10基因rs1800896位点可能为结核病的易感位点,与A等位基因携带者相比,携带G等位基因的个体结核病发病风险显著增高。
Objective To investigate the relationship between gene polymorphism of IL-10 gene-1082 G/A and susceptibility to tuberculosis.Methods Case-control family study was conducted,and the data was collected from Guangdong province.PCR-RFLP technique was used to detect the G/A polymorphism in the rs1800896 locus of IL-10 gene,and to analyze the distribution of genotypes and allele frequencies in case families and control families and their first-degree relatives.Logistic Regression Model was used to analyze the genetic variation and the risk of tuberculosis.Results A sample of 180 people was included.There were 28 cases in the family group(89 people),including 41 patients and 23 first-degree relatives and 35 cases in control family group(91 people).IL-10 gene loci rs1800896 genotype distribution was in line with Hardy-Weinberg law of genetic equilibrium(P>0.05),with good mass.The rs1800896 of the IL-10 gene may be a susceptibility factor to tuberculosis.Compared with the A allele of IL-10 gene rs1800896 carrier,the G allele was significantly over-represented in case groups(OR=4.48,95%CI=1.14-17.61),and the dominant model(AG+GG vs AA)was also associated with a high risk of tuberculosis(OR=4.48,95%CI=1.14-17.61).Conclusion The IL-10 gene rs1800896 may be a susceptible site to tuberculosis.Compared with the A allele carrier,the risk of tuberculosis in individuals carrying the G allele is significantly increased.
Objective To investigate the relationship between gene polymorphism of IL-10 gene-1082 G/A and susceptibility to tuberculosis.Methods Case-control family study was conducted,and the data was collected from Guangdong province.PCR-RFLP technique was used to detect the G/A polymorphism in the rs1800896 locus of IL-10 gene,and to analyze the distribution of genotypes and allele frequencies in case families and control families and their first-degree relatives.Logistic Regression Model was used to analyze the genetic variation and the risk of tuberculosis.Results A sample of 180 people was included.There were 28 cases in the family group(89 people),including 41 patients and 23 first-degree relatives and 35 cases in control family group(91 people).IL-10 gene loci rs1800896 genotype distribution was in line with Hardy-Weinberg law of genetic equilibrium(P>0.05),with good mass.The rs1800896 of the IL-10 gene may be a susceptibility factor to tuberculosis.Compared with the A allele of IL-10 gene rs1800896 carrier,the G allele was significantly over-represented in case groups(OR=4.48,95%CI=1.14-17.61),and the dominant model(AG+GG vs AA)was also associated with a high risk of tuberculosis(OR=4.48,95%CI=1.14-17.61).Conclusion The IL-10 gene rs1800896 may be a susceptible site to tuberculosis.Compared with the A allele carrier,the risk of tuberculosis in individuals carrying the G allele is significantly increased.
引文
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[14] Amirzargar AA,Rezaei N,Jabbari H,et al.Cytokine single nucleotide polymorphisms in Iranian patients with pulmonary tuberculosis[J].European Cytokine Network,2006,17(2):84-89.
[15] Ates ?,Musellim B,Ongen G,et al.Interleukin-10 and tumor necrosis factor-α gene polymorphisms in tuberculosis[J].Journal of Clinical Immunology,2008,28(3):232-236.
[16] Hu Y,Wu L,Li D,et al.Association between cytokine gene polymorphisms and tuberculosis in a Chinese population in Shanghai:a case-control study[J].BMC Immunology,2015,16:8.
[17] Henao MI,Montes C,París SC,et al.Cytokine gene polymorphisms in Colombian patients with different clinical presentations of tuberculosis[J].Tuberculosis,86(1):11-19.
[18] Joshi L,Chelluri LK,Valluri V,et al.Association of TNF-alpha,IL-10 and IL-6 promoter polymorphisms in pulmonary tuberculosis patients and their household contacts of younger age group[J].Comparative Immunology Microbiology and Infectious Diseases,2018,56:20-26.
[19] Oral HB,Budak F,Uzaslan EK,et al.Interleukin-10(IL-10)gene polymorphism as a potential host susceptibility factor in tuberculosis[J].Cytokine,2006,35(3/4):143-147.
[20] López-Maderuelo D,Arnalich F,Serantes R,et al.Interferon-gamma and interleukin-10 gene polymorphisms in pulmonary tuberculosis[J].American Journal of Respiratory and Critical Care Medicine,2003,167(7):970-975.
[21] Bellamy R,Ruwende C,Corrah T,et al.Assessment of the interleukin 1 gene cluster and other candidate gene polymorphisms in host susceptibility to tuberculosis[J].Tubercle and Lung Disease,1998,79(2):83-89.
[22] Asgharzadeh M,Ghorghanlu S,Rashedi JA,et al.Association of promoter polymorphisms of interleukin-10 and Interferon-Gamma genes with tuberculosis in azeri population of Iran[J].Iranian Journal of Allergy Asthma and Immunology,2016,15(3):167-173.
[2] Li QF,Zhang H,Yu L,et al.Down-regulation of Notch signaling pathway reverses the Th1/Th2 imbalance in tuberculosis patients[J].International Immunopharmacology,2018,54:24-32.
[3] 马志明,肖唐,林国,等.白介素-10基因多态性与肺结核病易感性的研究[J].广东医学,2007(8):1243-1245.
[4] 美朗曲措,扎多,黄丽萍,等.IL-10单核苷酸多态性检测及其与中国西藏藏族人群肺结核易感相关性研究[J].现代预防医学,2012,39(14):3607-3610.
[5] Liang L,Zhao YL,Yue J,et al.Interleukin-10 gene promoter polymorphisms and their protein production in pleural fluid in patients with tuberculosis[J].FEMS Immunology and Medical Microbiology,2011,62(1):84-90.
[6] Larsson L,Rymo L,Berglundh T.Sp1 binds to the G allele of the-1087 polymorphism in the IL-10 promoter and promotes IL-10 mRNA transcription and protein production[J].Genes and Immunity,2010,11(2):181-187.
[7] Liang B,Guo Y,Li Y,et al.Association between IL-10 gene polymorphisms and susceptibility of tuberculosis:evidence based on a meta-analysis[J].PLOS One,2014,9(2):e88448.
[8] Oral HB,Budak F,Uzaslan EK,et al.Interleukin-10(IL-10)gene polymorphism as a potential host susceptibility factor in tuberculosis[J].Cytokine,2006,35(3/4):143-147.
[9] Feng FM,Liu XX,Sun YH,et al.Independent and joint effects of the IL-6 and IL-10 gene polymorphisms in pulmonary tuberculosis among the Chinese Han population[J].Genetics and Molecular Research,2014,13(3):7766-7772.
[10] 沈福民.流行病学原理与方法[M].上海:上海医科大学出版社,2001.
[11] 郜艳晖,姜庆五,赵根明.病例对照家系设计中样本含量的估算[J].中国卫生统计,2003,20(6):344-346.
[12] Blischak JD,Tailleux L,Myrthil MA,et al.Predicting susceptibility to tuberculosis based on gene expression profiling in dendritic cells[J].Scientific Reports,2017,7(1):5702.
[13] Comstock GW.Tuberculosis in twins:a re-analysis of prophit survey[J].The American Review of Respiratory Disease,1978,117(4):621-624.
[14] Amirzargar AA,Rezaei N,Jabbari H,et al.Cytokine single nucleotide polymorphisms in Iranian patients with pulmonary tuberculosis[J].European Cytokine Network,2006,17(2):84-89.
[15] Ates ?,Musellim B,Ongen G,et al.Interleukin-10 and tumor necrosis factor-α gene polymorphisms in tuberculosis[J].Journal of Clinical Immunology,2008,28(3):232-236.
[16] Hu Y,Wu L,Li D,et al.Association between cytokine gene polymorphisms and tuberculosis in a Chinese population in Shanghai:a case-control study[J].BMC Immunology,2015,16:8.
[17] Henao MI,Montes C,París SC,et al.Cytokine gene polymorphisms in Colombian patients with different clinical presentations of tuberculosis[J].Tuberculosis,86(1):11-19.
[18] Joshi L,Chelluri LK,Valluri V,et al.Association of TNF-alpha,IL-10 and IL-6 promoter polymorphisms in pulmonary tuberculosis patients and their household contacts of younger age group[J].Comparative Immunology Microbiology and Infectious Diseases,2018,56:20-26.
[19] Oral HB,Budak F,Uzaslan EK,et al.Interleukin-10(IL-10)gene polymorphism as a potential host susceptibility factor in tuberculosis[J].Cytokine,2006,35(3/4):143-147.
[20] López-Maderuelo D,Arnalich F,Serantes R,et al.Interferon-gamma and interleukin-10 gene polymorphisms in pulmonary tuberculosis[J].American Journal of Respiratory and Critical Care Medicine,2003,167(7):970-975.
[21] Bellamy R,Ruwende C,Corrah T,et al.Assessment of the interleukin 1 gene cluster and other candidate gene polymorphisms in host susceptibility to tuberculosis[J].Tubercle and Lung Disease,1998,79(2):83-89.
[22] Asgharzadeh M,Ghorghanlu S,Rashedi JA,et al.Association of promoter polymorphisms of interleukin-10 and Interferon-Gamma genes with tuberculosis in azeri population of Iran[J].Iranian Journal of Allergy Asthma and Immunology,2016,15(3):167-173.