白细胞介素4受体基因多态性与支气管哮喘相关性
摘要
目的 探讨白细胞介素4受体(IL-4R)基因多态性与儿童支气管哮喘的相关性。方法：用聚合酶链反应／限制性片段长度多态性分析方法(PCR／RFLP)，检测30例哮喘儿童和30例正常对照儿童IL-4R Q576R的多态性，并用酶联免疫吸附法(ELISA)检测两组儿童血浆总IgE的水平，然后进行x~2检验及成组t检验。结果 1．IL-4R杂合突变基因型Q576R、突变等位基因R576的分布频率在哮喘儿童及正常对照儿童中差异有显著性，P＜0.05；2．哮喘儿童与正常儿童比较，血浆总IgE水平差异有显著性，P＜0.05；哮喘儿童中杂合突变基因型Q576R携带者与野生型Q576Q携带者比较，血浆总IgE水平差异没有显著性，P＞0.05。结论 1．IL-4R突变等位基因R576可能是儿童易感哮喘的一个候选基因；2．没有发现IL-4R等位基因R576对哮喘儿童血浆总IgE水平升高有明显影响。
objective To investigate the association of polymorphism in interleukin-4 receptor gene with childhood asthma. Methods 30 unrelated asthmatic children were included as experimental groups, 30 normal children who excluded atopic diseases were served as control groups .Then the polymorphism of IL-4R Q576R were determined by PCR/RFLP and the level of blood serum total IgE was tested by ELISA. Result 1. the distribution frequency of heterozygous genotype Q576R and mutant allele R576 was significantly higher in asthmatic children than normal controls, P<0.05; 2. The total IgE level was significantly different between the asthmatic children and control groups , P<0.05 ; 3 the level of serum IgE between the two groups who carry the genotype Q576R and Q576Q was not significantly different P>0.05. Conclusion 1. The mutant R576 allele of IL-4R may be one of the candidate genes for susceptibility to asthma ; Fail to find allele R576 had effect on the total serum IgE level in asthmatic children.
objective To investigate the association of polymorphism in interleukin-4 receptor gene with childhood asthma. Methods 30 unrelated asthmatic children were included as experimental groups, 30 normal children who excluded atopic diseases were served as control groups .Then the polymorphism of IL-4R Q576R were determined by PCR/RFLP and the level of blood serum total IgE was tested by ELISA. Result 1. the distribution frequency of heterozygous genotype Q576R and mutant allele R576 was significantly higher in asthmatic children than normal controls, P<0.05; 2. The total IgE level was significantly different between the asthmatic children and control groups , P<0.05 ; 3 the level of serum IgE between the two groups who carry the genotype Q576R and Q576Q was not significantly different P>0.05. Conclusion 1. The mutant R576 allele of IL-4R may be one of the candidate genes for susceptibility to asthma ; Fail to find allele R576 had effect on the total serum IgE level in asthmatic children.
引文
[1] Hakonarson H, Wjst M. Currem concepts on the genetics of asthma. Current opinion in pediatrics. 2001 Jun, 13(3); 267-277
[2] Nanavaty U, Goldstein AD, Levine SJ. Polymorphisms in Candidate Asthma Genes. The American Journal of The Medical Sciences, 2001 Jan, 321(1): 11-16
[3] Tsujimoto G Millennium. Project of MHLW. Nippon Rinsho, 2001, 59(10): 1884-8
[4] 曾林祥，周世良，况九龙，等．哮喘患者IgE高亲和力受体β链基因E237G突变的研究．江西医学院学报，2001，41(5)：43-45
[5] 伏瑾，成虹，胡良平，等．β2肾上腺素能受体基因多态性与哮喘及其临床表型的关系．中华医学遗传学杂志，2002Feb,19(1)：41-5
[6] 邱玉英，王祥，殷凯生．哮喘患者β2肾上腺素能受体基因的初步研究．南京医科大学学报，2000，20(1)：56-57
[7] 张嘉琳，成陈虹，胡良平等．白细胞介素4和白细胞介素10基因多态性与儿童哮喘的相关性及对细胞因子表达的影响．中华医学杂志，2002，20(2)：114-118
[8] 高金明，林耀广，邱长春，等．中国北方汉族人群人类白细胞抗原DQA1，-DQB1基因多态性与支气管哮喘遗传易感性的关系．中华医学杂志，2002，82(6)：379-383
[9] 白彦，林耀广，何维，等．支气管哮喘患者T细胞受体δ链多态性研究．中华结核和呼吸杂志，2001，24(4)：215-218
[10] 卢巍．白介素4与支气管哮喘．国外医学呼吸系统分册．2001，21(3)；125-129
[11] Steinke JW, Borish L. Th2 cytokines and asthma. Intedeukin-4: its role in the pathogenesis of asthma, and targeting it for asthma treatment with interleukin-4 receptor antagonists. Respir Res.2001,2(2): 66-70
[12] Shirakawa T, Deichmann KA, Izhhara K, et al. Atopy and asthma genetic variants of IL-4 and IL-13 signalling.Immunol Today,2000,21(2): 608
[13] Deichmann K, Bardutzky J, Forster J, et al. Common polymorphisms in the coding part of the IL-4 receptor. Biochemical and Biophysical Research Communication, 1997, 231(3)696-7
[14] Hershey GK, Friedrich M.F, Esswein L.A, et al. The association of atopy with a gain-of-fuction mutation in the α subunit of the interleukin-4 receptor. The New England J of Medicine, 1997, 337(24): 1720-5
[15] Rosa-Rosa. L, Zimmermann N , Bernstein JA, et al. The 576R IL-4 receptor α allele correlates with asthma severity. J Allergy Clin Immunol, 1999, 104(5): 1008-1014
[16] 全国儿科哮喘防治协作组．儿童哮喘防治常规(试行)．中华儿科杂志，1998，12(12)：747-751
[17] Aithal GP, Day CP, Leathert J, et al. Association of single nucleotide polymorphisms in the interlukin-4 gene and intedeukin-4 receptor gene with Crohn's disease in a British population Genes and Immunity ,2001, 2: 44-47
[18] Wjst M, kruse S, Illig T, et al. Asthma and IL-4 receptor alpha gene variants Hum Immunol, 2001, 62(11): 1251
[19] Sandford A, Chagani T, zhu shoukang et al. Polymorphisms inthe IL-4,IL-4Rα and FCERIB genes and asthma severity J Allergy clin Immunol, 2000,106(1): 135-140
[20] Mitsuyasu H, Yanagihara Y, Mao XQ, et al. Cutting Edge: Dominnant Effect of Ile50Val Variant of the Human IL-4 Receptor a Chain in IgE Synthesis. The Journal of Immunology, 1998, 19(2)1227-1231
[21] Grimbacher B,Holland SM, Puck JM. The interlukin-4 receptor variant Q675R in hyper-IgE syndrome. N Engl J Med,1998, 338(15): 1073-1074
[22] 李明华，殷凯生，朱栓立主编．哮喘病学．北京：人民卫生出版社，1998．第一版，25-35
[23] Marsh D G;. Neely JD, Breazeale DR, et al. Linkage Analysis of IL-4 and Other chromosome 5q31.1 markers and total serum immunoglobulin E concentrations Science, 1994, Vol264: 1152-1155
[24] Hizawa N, Yamaguchi E, Jinushi E, et al. A common FCERIB gene promoter polymorphism influences total serum IgE levels in a Japanese population. Am J Respir Crit Care Med, 2000 Mar,161(3 Pt 1):906-9
[25] Deichmann KA, Heinzann A, Forster J. et al. Linkage and allelic associationof atopy and marker franking the IL-4 receptor gene. Clin Exp Allergy, 1998, 28(2): 151-5
[26] 陈竺 主编．医学遗传学．北京：人民卫生出版社：2001，83
[27] Risma KA, Wang N, Andrews RP, et al. IL-4 receptor alpha is associated with allergic asthma and enhanced IL-4receptor function.Immunol, 2002 Aug, 69(3): 1604-10
[28] Hall IP. Interleukin-4 receptor alpha gene variants and allergic disease. Respir Res. 2000, 1(1): 1-8
[29] Tan EC, Lee BW, Tay AWN, et al. interleukin -4 receptor variant Q576R: ethnic differences and association with atopy Clin Genet,1999,56(4): 333-334
[2] Nanavaty U, Goldstein AD, Levine SJ. Polymorphisms in Candidate Asthma Genes. The American Journal of The Medical Sciences, 2001 Jan, 321(1): 11-16
[3] Tsujimoto G Millennium. Project of MHLW. Nippon Rinsho, 2001, 59(10): 1884-8
[4] 曾林祥，周世良，况九龙，等．哮喘患者IgE高亲和力受体β链基因E237G突变的研究．江西医学院学报，2001，41(5)：43-45
[5] 伏瑾，成虹，胡良平，等．β2肾上腺素能受体基因多态性与哮喘及其临床表型的关系．中华医学遗传学杂志，2002Feb,19(1)：41-5
[6] 邱玉英，王祥，殷凯生．哮喘患者β2肾上腺素能受体基因的初步研究．南京医科大学学报，2000，20(1)：56-57
[7] 张嘉琳，成陈虹，胡良平等．白细胞介素4和白细胞介素10基因多态性与儿童哮喘的相关性及对细胞因子表达的影响．中华医学杂志，2002，20(2)：114-118
[8] 高金明，林耀广，邱长春，等．中国北方汉族人群人类白细胞抗原DQA1，-DQB1基因多态性与支气管哮喘遗传易感性的关系．中华医学杂志，2002，82(6)：379-383
[9] 白彦，林耀广，何维，等．支气管哮喘患者T细胞受体δ链多态性研究．中华结核和呼吸杂志，2001，24(4)：215-218
[10] 卢巍．白介素4与支气管哮喘．国外医学呼吸系统分册．2001，21(3)；125-129
[11] Steinke JW, Borish L. Th2 cytokines and asthma. Intedeukin-4: its role in the pathogenesis of asthma, and targeting it for asthma treatment with interleukin-4 receptor antagonists. Respir Res.2001,2(2): 66-70
[12] Shirakawa T, Deichmann KA, Izhhara K, et al. Atopy and asthma genetic variants of IL-4 and IL-13 signalling.Immunol Today,2000,21(2): 608
[13] Deichmann K, Bardutzky J, Forster J, et al. Common polymorphisms in the coding part of the IL-4 receptor. Biochemical and Biophysical Research Communication, 1997, 231(3)696-7
[14] Hershey GK, Friedrich M.F, Esswein L.A, et al. The association of atopy with a gain-of-fuction mutation in the α subunit of the interleukin-4 receptor. The New England J of Medicine, 1997, 337(24): 1720-5
[15] Rosa-Rosa. L, Zimmermann N , Bernstein JA, et al. The 576R IL-4 receptor α allele correlates with asthma severity. J Allergy Clin Immunol, 1999, 104(5): 1008-1014
[16] 全国儿科哮喘防治协作组．儿童哮喘防治常规(试行)．中华儿科杂志，1998，12(12)：747-751
[17] Aithal GP, Day CP, Leathert J, et al. Association of single nucleotide polymorphisms in the interlukin-4 gene and intedeukin-4 receptor gene with Crohn's disease in a British population Genes and Immunity ,2001, 2: 44-47
[18] Wjst M, kruse S, Illig T, et al. Asthma and IL-4 receptor alpha gene variants Hum Immunol, 2001, 62(11): 1251
[19] Sandford A, Chagani T, zhu shoukang et al. Polymorphisms inthe IL-4,IL-4Rα and FCERIB genes and asthma severity J Allergy clin Immunol, 2000,106(1): 135-140
[20] Mitsuyasu H, Yanagihara Y, Mao XQ, et al. Cutting Edge: Dominnant Effect of Ile50Val Variant of the Human IL-4 Receptor a Chain in IgE Synthesis. The Journal of Immunology, 1998, 19(2)1227-1231
[21] Grimbacher B,Holland SM, Puck JM. The interlukin-4 receptor variant Q675R in hyper-IgE syndrome. N Engl J Med,1998, 338(15): 1073-1074
[22] 李明华，殷凯生，朱栓立主编．哮喘病学．北京：人民卫生出版社，1998．第一版，25-35
[23] Marsh D G;. Neely JD, Breazeale DR, et al. Linkage Analysis of IL-4 and Other chromosome 5q31.1 markers and total serum immunoglobulin E concentrations Science, 1994, Vol264: 1152-1155
[24] Hizawa N, Yamaguchi E, Jinushi E, et al. A common FCERIB gene promoter polymorphism influences total serum IgE levels in a Japanese population. Am J Respir Crit Care Med, 2000 Mar,161(3 Pt 1):906-9
[25] Deichmann KA, Heinzann A, Forster J. et al. Linkage and allelic associationof atopy and marker franking the IL-4 receptor gene. Clin Exp Allergy, 1998, 28(2): 151-5
[26] 陈竺 主编．医学遗传学．北京：人民卫生出版社：2001，83
[27] Risma KA, Wang N, Andrews RP, et al. IL-4 receptor alpha is associated with allergic asthma and enhanced IL-4receptor function.Immunol, 2002 Aug, 69(3): 1604-10
[28] Hall IP. Interleukin-4 receptor alpha gene variants and allergic disease. Respir Res. 2000, 1(1): 1-8
[29] Tan EC, Lee BW, Tay AWN, et al. interleukin -4 receptor variant Q576R: ethnic differences and association with atopy Clin Genet,1999,56(4): 333-334
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