支气管哮喘患儿白介素1受体1基因RS1041973及RS10208293位点单核苷酸多态性观察
摘要
目的观察支气管哮喘患儿白介素1受体1(Interleukin 1 receptor-like 1,IL1RL1)基因RS1041973、RS10208293位点的单核苷酸多态性。方法 86例哮喘患儿为哮喘组,100例健康婴幼儿为对照组,收集两组外周血,ARMS-qPCR法检测分析IL1RL1基因RS1041973、RS10208293位点的基因型和等位基因。结果哮喘组IL1RL1基因RS1041973位点基因型AA、AC、CC的分布频率分别为3. 5%(3/86)、23. 3%(20/86)、73. 2%(63/86),等位基因A、C的分布频率分别为15. 2%(26/172)、84. 8%(146/172);对照组分别为8. 0%(8/100)、26. 0%(26/100)、66. 0%(66/100)、21%(42/200)、79%(158/200);两组AC、CC基因型分布频率及等位基因A、C的分布频率差异存在统计学意义(P均<0. 05)。与RS1041973位点基因型AA基因人群比较,RS1041973位点AC、CC基因型的个体患支气管哮喘的风险性增加(校正OR=1. 769,2. 212; 95%CI:0. 47～6. 655,0. 637～7. 687);且携带C等位基因的个体患支气管哮喘的危险度是A基因的1. 506倍(95%CI:0. 726～3. 126,P <0. 05)。哮喘组IL1RL1基因RS10208293位点基因型AA、AG、GG的分布频率分别为4. 6%(4/86)、25. 6%(22/86)、69. 8%(60/86),等位基因A、G的分布频率分别为17. 4%(30/172)、82. 6%(142/172);对照组分别为7. 0%(7/100)、29. 0%(29/100)、64. 0%(64/100)、21. 5%(43/200)、78. 5%(157/200);两组AG、GG基因型分布频率及等位基因A、G的分布频率差异存在统计学意义(P均<0. 05)。与RS10208293位点基因型AA基因人群比较,RS10208293位点AG、GG基因型的个体患哮喘的风险性增加(校正OR=1. 255,1. 531; 95%CI:0. 355～-4. 442,0. 463～-5. 067);且携带G等位基因的个体患哮喘的危险度是A基因的1. 36倍(95%CI:0. 673～2. 749,P <0. 05)。结论支气管哮喘患儿IL1RL1基因RS1041973位点C等位基因、RS10208293位点G等位基因突变频率较高。IL1RL1基因RS1041973位点A/C的C等位基因、RS10208293位点A/G的G等位基因的突变可能与支气管哮喘的易感性有关。
引文
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[2]Boulet LP,Fitz Gerald JM,Reddel HK.The revised 2014 GINAstrategy report:o-pportunities for change[J].Curr Opin Pulm Med,2015,21(1):1-7.
[3]Mersha TB,Martin LJ,Myers JMB,et al.Genomic architecture of asthma differs by sex[J].Genomics,2015,106(1):15-22.
[4]Altmuller J,Seidel C,Lee YA,et al.Phenotypic and genet-ic heterogeneity in a genome-wide linkage study of asthma families[J].Bmc Pulm Med,2005,5(1):1-8.
[5]Wang J,Simayi M,Wushouer Q,et al.Association between polymorphisms in ADAM33,CD14,and TLR4 with asthma in the Uygur population in China.[J].Genet Mol Res,2014,13(2):4680-4690.
[6]Torgerson DG,Ampleford EJ.Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations[J].Nat Genet,2011,43(9):887-892.
[7]陈杰斌,张洁.RAD50,IL-33和IL1RL1基因与汉族人群过敏性哮喘相关性[J].实用临床医学杂志,2017,21(5):97-101.
[8]中华医学会儿科学分会呼吸学组,《中华儿科杂志》编辑委员会.儿童支气管哮喘诊断与防治指南(2016年版)[J].中华儿科杂志,2016,54(3):167-181.
[9]Wongratanacheewin S.Update of cytokines and genes in asthma and allergic rhinitis.[J].Asian Pac J Allergy Immunol,2014,32(4):275.
[10]Díaz-Jiménez D,Núez L,De la Fuente M,et al.A functional IL1RL1 variant regulates corticosteroid-induced s ST2 expression in ulcerative colitis[J].Sci Rep,2017,7(1):10180.
[11]Lott JM,Sumpter TL,Turnquist HR.New dog and new tricks:evolving roles for IL-33 in type 2 immunity[J].J Leukoc Biol,201597(6):1037-1048.
[12]Louten J,Rankin AL,Li Y,et al.Endogenous IL-33 enhances Th2 cytokine production and T-cell responses during allergic airway inflammation[J].Int Immunol,2011,23(5):307-315.
[13]Svenningsen S,Nair P.Asthma endotypes and an overview of targeted therapy for asthma[J].Frontiers in Medicine,2017,4(9):158.
[14]Haeper RW,Zeki AA.Immunobiology of the critical astrhma syndrome[J].Clin Rev Allergy Immunol,2015,48(1):54-65.
[15]Thomas C,Bazan JF,Garcia KC.Structure of the activating IL-1receptor signal-ing complex[J].Nat Struct Mol Biol,2012,19(4):455-457.