目的 研究CTLA-4基因多态性与儿童支气管哮喘易感性及外周血IFN-γ、IL-4和IgE的关系,为儿童支气管哮喘的诊断及治疗提供理论及临床依据。方法 2017年4月-2019年2月选择郑州大学第三附属医院儿童支气管哮喘患者78例为病例组,健康体检的正常儿童67例作为对照组,检测两组CTLA-4 基因的rs231725单核苷酸多态性,同时检测病例组外周血IFN-γ、IL-4、IgE水平。结果 病例组CTLA-4 rs231725 AA基因型比例高于对照组(66.7% vs. 19.4%),CTLA-4 rs231725 GG基因型比例低于对照组(19.3% vs. 73.2%)(P<0.05);病例组CTLA-4 rs231725 A等位基因频率比例高于对照组(73.7% vs. 23.1%)(P<0.05),CTLA-4 rs231725 G等位基因频率比例低于对照组(26.3% vs. 76.9%)(P<0.05);CTLA-4 rs231725 AG基因型IFN-γ、IL-4、IgE水平均高于GG基因型,差异有统计学意义(P<0.05);CTLA-4 rs231725各基因型及等位基因频率与有无支气管哮喘伴泌尿系统损害、支气管哮喘伴消化道反应无明显相关关系(P>0.05);CTLA-4 rs231725 AA基因型(OR=2.625,95%CI=1.273~5.138)及A等位基因频率(OR=1.987,95%CI=1.121~3.397)与支气管哮喘伴肾炎相关关系明显(P<0.05)。结论 CTLA-4 rs231725 AA基因型和A等位基因均与儿童支气管哮喘易感性增加相关;高水平的IFN-γ、IL-4、IgE可能是CTLA-4 rs231725 AA基因支气管哮喘易感性增强的原因。
Abstract
Objective To explore the relationship between CTLA-4 gene polymorphism and susceptibility to bronchial asthma in children and peripheral blood IFN-γ, IL-4 and IgE, and provide theoretical and clinical basis for the diagnosis and treatment of bronchial asthma in children. Methods From April 2017 to February 2019,78 children with bronchial asthma in the Third Affiliated Hospital of Zhengzhou University were in the case group, and 67 healthy children in the physical examination were used as the control group.The rs231725 single nucleotide polymorphism of CTLA-4 gene was detected in both groups, and the levels of IFN-γ, IL-4 and IgE in peripheral blood of the case group were also detected. Results The proportion of CTLA-4 rs231725 AA genotype was higher in the case group than in the control group (66.7% vs 19.4%), and the proportion of CTLA-4 rs231725 GG genotype was lower than that in the control group (19.3% vs 73.2%) (P<0.05); CTLA-4 rs231725 A allele frequency ratio was higher than in the control group (73.7% vs 23.1%) (P<0.05), and the CTLA-4 rs231725 G allele frequency ratio was lower than in the control group (26.3% vs 76.9%) (P <0.05); CTLA-4 rs231725 AG genotype IFN-γ, IL-4, IgE levels were higher than GG genotype, and the differences were statistically significant (P<0.05); At CTLA-4 rs231725 genotypes and allele frequencies, there were no significant correlation between bronchial asthma and urinary system damage, bronchial asthma with digestive tract reaction (P>0.05).CTLA-4 rs231725 AA genotype(OR=2.625,95%CI=1.273-5.138) and A allele(OR=1.987,95%CI=1.121-3.397) frequencie were associated with bronchial asthma with nephritis(P<0.05). Conclusion CTLA-4 rs231725 AA genotype and A allele are associated with increased susceptibility to bronchial asthma in children, which may be caused by the high levels of IFN-γ, IL-4, and IgE.
关键词
CTLA-4基因多态性 /
支气管哮喘 /
易感性 /
IFN-γ /
IL-4 /
IgE
Key words
CTLA-4 gene polymorphism /
bronchial asthma /
susceptibility /
IFN-γ /
IL-4 /
IgE
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参考文献
[1] Uwaezuoke SN, Ayuk AC, Eze JN.Severe bronchial asthma in children:a review of novel biomarkers used as predictors of the disease[J].J Asthma Allergy,2018,11:11-18.
[2] Hayashi F, Hayashi S,Matsuse D, et al.Hopkins syndrome following the first episode of bronchial asthma associated with enterovirus D68:a case report[J].BMC Neurology,2018,18(1):71.
[3] Li F, Zhu Y,Xie X, et al.Interleukin-12B gene polymorphisms and bronchial asthma risk:a meta-analysis[J].J Asthma,2017,54(8):777-783.
[4] Elmaraghy MA, Hodieb MM, Khattab RAER, et al.Association between TSLP gene polymorphism and bronchial asthma in children in Beni Suef Governorate in Egypt[J].Comp Clin Pathol,2018,27(3):565-570.
[5] Borel P, Desmarchelier C, Nowicki M, et al.A combination of single-nucleotide polymorphisms is associated with interindividual variability in dietary β-carotene bioavailability in healthy men[J].J Nutr,2015,145(8):1740-1747.
[6] Chen S, Wang Y, Yu C, et al.Investigation of cytotoxic T-lymphocyte antigen-4polymorphisms in non-small cell lung cancer:a case-control study[J].Oncotarget,2017,8(44):76634-76643.
[7] Tian L,Xie XH, Zhu ZH.Calotropin regulates the apoptosis of non small cell cancer by regulating the cytotoxic T lymphocyte associated antigen 4 mediated TGF β/ERK signaling pathway[J].Mol Med Rep,2018,17(6):7683-7691.
[8] Zhang F,Rong Z, Wang Z, et al.Periostin promotes ectopic osteogenesis of CTLA4-modified bone marrow mesenchymal stem cells[J].Cell Tissue Res,2017,370(1):143-151.
[9] Sueda S, Nakayama S, Adachi T, et al.Cytotoxic T-lymphocyte-associated antigen 4-positive aggressive adult T cell leukemia/lymphoma[J].Ann Hematol,2019,98(1):235-236.
[10] 中华医学会呼吸病学分会哮喘学组.支气管哮喘防治指南(2016年版)[J].中华结核和呼吸杂志,2016,39(9):675-697.
[11]Wei SC, Levine JH, Cogdill AP, et al.Distinct cellular mechanisms underlie Anti-CTLA-4 and Anti-PD-1 checkpoint blockade[J].Cell,2017,170(6):1120-1133.
[12] Zhang Y, Zhang S, Xia W, et al.Association of cytotoxic T-lymphocyte antigen 4 rs231775 gene polymorphism with colorectal cancer risk[J].J Cancer ResTher,2018,14(Suppl):526-532.
[13] Zhang C, Peng Y,Hublitz P, et al.Genetic abrogation of immune checkpoints in antigen-specific cytotoxic T-lymphocyte as a potential alternative to blockade immunotherapy[J].Sci Rep-UK,2018,8(1):5549.
[14] Tian L,Xie XH, Zhu ZH.Calotropin regulates the apoptosis of non small cell cancer by regulating the cytotoxic T lymphocyte associated antigen 4 mediated TGF β/ERK signaling pathway[J].Mol Med Rep,2018,17(6):7683-7691.
[15] Shih YL, Lu HF, Hsiao CW, et al.Distribution of cytotoxic T lymphocyte-associated antigen-4 promoter polymorphisms in Taiwanese patients with type 2 diabetes mellitus[J].Int J Med Sci,2018,15(4):395-402.
[16] Durgeau A, Virk Y, Corgnac S, et al.Recent advances in targeting CD8 T-cell immunity for more effective cancer immunotherapy[J].Front Immunol,2018,9:14.
[17] Mishra OP, Chhabra P, Narayan G, et al.Cytotoxic T-lymphocyte antigen-4 (CTLA4) gene expression and urinary CTLA4 levels in idiopathic nephrotic syndrome[J].Indian J Pediatr,2019,86(1):26-31.
[18] Wang P, Zhao P, Dong S, et al.An albumin-binding polypeptide both targets cytotoxic T lymphocyte vaccines to lymph nodes and boosts vaccine presentation by dendritic cells[J].Theranostics,2018,8(1):223-236.
[19] Zheng Y, Wang H, Luo L, et al.A meta-analysis of the association between CTLA-4 genetic polymorphism and susceptibility of asthma[J].Medicine,2018,97(28):e11380.
[20] Zhang Y, Sun E, Li X, et al.miR-155 contributes to Df1-induced asthma by increasing the proliferative response ofTh cells via CTLA-4 downregulation[J].Cell Immunol,2017,314:1-9.
基金
河南省医学科技攻关计划项目(201703219)