198例哮喘儿童遗传易感性研究

郑伯强; 王桂兰; 杨赛; 鲁衍强; 刘睿俊; 李瑛

PDF(872 KB)

中国当代儿科杂志 ›› 2012, Vol. 14 ›› Issue (11) : 811-814.

论著·临床研究

198例哮喘儿童遗传易感性研究

郑伯强，王桂兰，杨赛，鲁衍强，刘睿俊，李瑛

作者信息 +

Study of genetic susceptibility in 198 children with asthma

ZHENG Bo-Qiang, WANG Gui-Lan, YANG Sai, LU Yan-Qiang, LIU Rui-Jun, LI Ying

Author information +

文章历史 +

摘要

目的：分析4种哮喘相关基因位点在198例哮喘患儿中的单核苷酸多态性（single nucleotide polymorphismr，SNP）分布特点，并探讨其与儿童哮喘遗传易感性及某些哮喘临床表型的关系。方法：采用聚合酶链反应产物电泳鉴定法及实时荧光定量核酸扩增技术检测4种哮喘相关基因位点SNP在198名哮喘患儿和110名健康对照者中的分布，并测定哮喘患儿的血清总IgE（TIgE）水平及血嗜酸性粒细胞比例（%EOS），同时对4种哮喘相关基因位点不同基因型间的TIgE及%EOS分别进行比较分析。结果：血管紧张素转换酶（ACE）基因位点纯合子基因型（DD）频率在哮喘组明显高于健康对照组（χ2=30.667，P＜0.01），且D型等位基因频率在哮喘组亦明显高于健康对照组（χ2=7.151，P<0.01）；各基因位点多态性分布与血清TIgE水平及%EOS均无相关性（均P＞0.05）。结论：ACE基因DD基因型与儿童哮喘的遗传易感性有关，可能是儿童哮喘的危险因素。

Abstract

OBJECTIVE: To analyze the frequency distribution of single nucleotide polymorphisms (SNPs) of four asthma-related gene loci (ACE I/D; ADRB2 Arg16Gly; TNF-α G-308A; MS4A2 Glu237Gly) in 198 asthmatic children, and to investigate its association with genetic susceptibility to childhood asthma and some clinical phenotypes of asthma. METHODS: Polymerase chain reaction product electrophoresis identification and real-time quantitative PCR detecting system were used to determine the frequency distributions of the SNPs of the four asthma-related gene loci in 198 asthmatic children and 110 healthy controls. The serum total IgE (TIgE) levels and blood eosinophil proportion (%EOS) of the asthmatic children were measured. Different genotypes at the four asthma-related gene loci were compared in terms of TIgE and %EOS. RESULTS: The genotype DD of angiotensin-converting enzyme (ACE) had a significantly higher frequency in the asthmatic children than in the healthy controls (χ2= 30.667, P0.05). CONCLUSIONS: Genotype DD of ACE is related to genetic susceptibility to childhood asthma and may be the risk factor for childhood asthma.

导出引用

郑伯强，王桂兰，杨赛，鲁衍强，刘睿俊，李瑛. 198例哮喘儿童遗传易感性研究[J]. 中国当代儿科杂志. 2012, 14(11): 811-814

ZHENG Bo-Qiang, WANG Gui-Lan, YANG Sai, LU Yan-Qiang, LIU Rui-Jun, LI Ying. Study of genetic susceptibility in 198 children with asthma[J]. Chinese Journal of Contemporary Pediatrics. 2012, 14(11): 811-814

中图分类号： R562.2+5

参考文献

［1］Beasley R. The burden of asthma with specific reference to the United States［J］. J Allergy Clin Immunol, 2002, 109(5 Suppl): S482-S489.

［2］Zhang J, Paré PD, Sandford AJ. Recent advances in asthma genetics［J］. Respir Res, 2008, 9: 4.

［3］Masoli M, Fabian D, Holt S, Beasley R; Global Initiative for Asthma (GINA) Program. The global burden of asthma: executive summary of the GINA Dissemination Committee report［J］. Allergy, 2004, 59(5): 469-478.

［4］全国儿童哮喘防治协作组. 中国城区儿童哮喘患病率调查.中华儿科杂志,2003,41(2):123127.

［5］中华医学会儿科学分会呼吸学组.儿童支气管哮喘诊断与防治指南［J］.中华儿科杂志, 2008,46(10):745-753.

［6］Weiss ST, Raby BA, Rogers A. Asthma genetics and genomics 2009［J］. Curr Opin Genet Dev, 2009, 19(3): 279-282.

［7］LeeYC, Cheon KT, Lee HB, Kim W, Rhee YK, Kim DS.Gene polymorphisms of endothelial nitric oxide synthase and angiotensin-converting enzyme in patients with asthma［J］. Allergy, 2000, 55(10): 959963.

［8］Tomita H, Sawto S, Matsuda R, Ogisu N, Mori T, Niimi T, et al. Genetic polymorphism of the angiotensin-converting enzyme (ACE) in asthmatic patients［J］. Respir Med, 1998, 92(12): 1305-1310.

［9］Gao J, Lin Y, Xiao Y, Xu K, Xu W, Zhu Y, et al. Polymorphism of angiotensin converting enzyme gene and genetic susceptibility to asthma with familial aggregation［J］. Chin Med Sci J, 2000, 15(1): 24-28.

［10］Urhan M, Degirmerci I, Harmanci E, Gunes HV, Metintas M, Basaran A. High frequency of DD polymorphism of the angiotensin-converting enzyme gene in Turkish asthmatic patients［J］. Allergy Asthma Proc, 2004, 25(4): 243-247.

［11］Vercelli D. Discovering susceptibility genes for asthma and allergy［J］. Nat Rev Immunol, 2008, 8(3): 169-182.

［12］高光凯,王士雯,张进川.中国北方汉族人群支气管哮喘患者β2肾上腺素能受体基因多态性研究［J］.中华结核和呼吸杂志.2000,23(2):93-97.

［13］Ober C, Hoffjan S. Asthmagenetics 2006: the long and winding road to gene discovery［J］. Genes Immun, 2006, 7(2): 95-100.

［14］Hill MR, Cookson WO. A new variant of the beta subunit of the high-affinity receptor for immunoglobulin E(Fc epsilon RI beta E237G): associations with measures of atopy and bronchial hyper-responsiveness［J］.Hum Mol Genet, 1996, 5(7): 959-962.

［15］Shirakawa T, Mao XQ, Sasaki S, Enomoto T, Kawai M, Morimoto K, et al. Association between atopic asthma and a coding variant of Fc epsilon RI beta in a Japanese population［J］. Hum Mol Genet, 1996, 5(8): 1129-1130.

［16］Raby BA, Soto-Quiros ME, Avila L, Lake SL, Murphy A, Liang C, et al. Sex-specific linkage to total serum immunoglobulin E in families of chileren with asthma in Costa Rica［J］. Hum Mol Genet, 2007, 16(3): 243-253.

［17］Deware JC, Wilkinson J, Wheatley A, Thomas NS, Doull I, Morton N, et al. The glutamine 27 β2-adrenoceptor polymorphism is associated with elevated IgE levels in asthmatic families［J］. J Allergy Clin Immunol, 1997, 100(2): 261-265.

［18］Weidinger S, Gieger C, Rodriguez E, Baurecht H, Mempel M, Klopp N, et al. Genome-wide scan on total serum IgE levels identifies FCER1A as novel susceptibility locus［J］.PloS Genet, 2008, 4(8): el000166.

［19］Nagarkatti R, B-Rao C, Vijayan V, Sharma SK, Ghosh B. Signal transducer and activator of transcription 6 haphotypes and asthma in the Indian population［J］. Am J Respir Cell Mol Biol, 2004, 31(3): 317321.

［20］Zhang Y, Leaves NI, Anderson GG, Ponting CP, Broxholme J, Holt R, et al. Positional cloning of a quantitative trait locus on chromosome 13q14 that influence immunoglobulin E levels and asthma［J］. Nat Genet, 2003, 34(2): 181-186.

［21］张爱民,李海林,郝萍,陈燕华,李继梅,莫亚雄，等. 白细胞介素4受体Q576R基因多态性与支气管哮喘病人IgE的相关性［J］.中国当代儿科杂志, 2006,8(2):109-112.

［22］张喜英,赵文利,桂芹,何念海.β2-肾上腺素能受体基因多态性与儿童哮喘的关系［J］.临床儿科杂志, 2008,26(5) :399-402, 408.