白細胞介素10 基因單核苷酸多態性與哮喘遺傳易感性的相關性研究_《中國呼吸與危重監護雜志》

作者：

楊學習 ¹ , 李粉霞 ¹ , 李欣 ¹ , 孫靜哲 ¹ , 孫敏英 ¹ ,  李明 ^1,2

1 南方醫科大學生物技術學院抗體工程研究所( 廣東廣州 510515) ;;
2 中山大學達安基因股份有限公司( 廣東廣州 510665) 基金項目: 廣州市科技攻關計劃( 編號: 2008A1-E4151);

關鍵詞：

白細胞介素10 單核苷酸多態性哮喘

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目的探討白細胞介素10 ( IL-10) 基因三個單核苷酸多態性位點( rs1800896、rs3024496 和rs3024492) 與哮喘遺傳易感性的相關性。方法應用基質輔助激光解吸附電離飛行時間質譜( MALDI-TOF-MS) 平臺及MassARRAY-IPLEX 技術, 分別對廣州地區漢族人群中275 例正常對照組和302 例哮喘患者組IL-10 三個單核苷酸多態性位點( rs1800896、rs3024496 和rs3024492) 進行基因分型并分析兩組間分布情況。用Χ2 檢驗統計分析病例組和對照組基因型和等位基因的頻率;采用非條件Logistic 回歸分析, 校正性別、年齡影響, 計算比數比( OR) 和95% 可信區間( CI) , 評價多態性位點與哮喘遺傳易感性的相關性。結果 ① rs1800896 位點在廣州地區漢族人群中存在GG、GA、AA 三種多態性, 其總分布頻率分別為2. 12% 、39. 65% 、58. 23% , 攜帶GA 雜型者患哮喘的危險性高于AA 基因型者。②rs3024492 位點在廣州地區漢族人群中只存在AA 和AT 兩種基因型, 其總
分布頻率分別為1. 22% 和98. 78% , 該位點的多態性與哮喘的易感性無關。③rs3024496 位點在廣州地區漢族人群中也只存在TT 和CT 兩種基因型, 其總分布頻率分別為90. 59% 和9. 41% , 該位點的多態性與哮喘的易感性無關。結論在IL-10 三個單核苷酸多態性位點中, rs1800896 與哮喘的易感性顯著相關, 而rs3024492 和rs3024496 與哮喘的易感性不相關

引用本文： 楊學習,李粉霞,李欣,孫靜哲,孫敏英,李明. 白細胞介素10 基因單核苷酸多態性與哮喘遺傳易感性的相關性研究. 中國呼吸與危重監護雜志, 2010, 9(5): 485-489. doi: 復制

1.	Becklake MR, Ernst P. Environmental factors. Lancet, 1997 , 350 Suppl 2 : SII10 -13.
2.	Newman-Taylor A. Environmental determinants of asthma. Lancet,1995, 345: 296-299.
3.	Akdis CA, Joss A, Akdis M, et al. Mechanism of IL-10-induced T cell inactivation in allergic inflammation and normal response to allergens. Int Arch Allergy Immunol, 2001, 124: 180-182.
4.	Palmer LJ, Celedón JC, Chapman HA, et al. Genome-wide linkage analysis of bronchodilator responsiveness and post-bronchodilator spirometric phenotypes in chronic obstructive pulmonary disease.Hum Mol Genet, 2003 , 12: 1199-1210.
5.	Eskdale J, Gallagher G, Verweij CL, et al. Interleukin 10 secretion in relation to human IL-10 locus haplotypes. Proc Natl Acad Sci USA, 1998, 95: 9465-9470.
6.	Rosenwasser LJ, Borish L. Genetics of atopy and asthma: the rationale behind promoter-based candidate gene studies ( IL-4 and IL-10) . Am J Respir Crit Care Med, 1997, 156: S152-S155.
7.	Lim S, Crawley E, Woo P, et al. Haplotype associated with low interleukin-10 production in patients with severe asthma. Lancet,1998, 352 : 113.
8.	張嘉琳, 陳虹, 胡良平, 等. 白細胞介素4 和10 基因多態性與兒童哮喘的相關性及對細胞因子表達的影響. 中華醫學雜志,2002, 82: 114-118 .
9.	Jurinke C, van den Boom D, Cantor CR, et al. Automated genotyping using the DNA MassArray technology. Methods Mol Biol, 2001 , 170: 103-116.
10.	Leushner J, Chiu NH. Automated mass spectrometry: a revolutionary technology for clinical diagnostics. Mol Diagn, 2000 ,5 : 341-348.
11.	Lyon H, Lange C, Lake S, et al. IL-10 gene polymorphisms are associated with asthma phenotypes in children. Genet Epidemiol,2004 , 26 : 155-165 .
12.	Hang LW, Hsia TC, Chen WC, et al. Interleukin-10 gene -627 allele variants, not interleukin-I beta gene and receptor antagonist gene polymorphisms, are associated with atopic bronchial asthma. J Clin Lab Anal, 2003, 17 : 168-173.
13.	Karjalainen J, Hulkkonen J, Nieminen MM, et al. Interleukin-10 gene promoter region polymorphism is associated with eosinophil count and circulating Immunoglobulin E in adult asthma. Clin Exp Allergy, 2003, 33: 78-83 .
14.	Chatterjee R, Batra J, Kumar A, et al. Interleukin-10 promoter polymorphisms and atopic asthma in North Indians. Clin Exp Allergy, 2005, 35: 914-919.
15.	Hobbs K, Negri J, KlinnertM, et al. Interleukin-10 and transforming growth factor-beta promoter polymorphisms in allergies and asthma.Am J Respir Crit Care Med, 1998 , 158: 1958 -1962 .
16.	http: / /hapmap. ncbi. nlm. nih. gov/ cgi-perl / snp_ details _ phase3 ?name = rs1800896&source = hapmap27 _ B36&tmpl = snp_ details _phase3 .
17.	http: / /hapmap. ncbi. nlm. nih. gov/ cgi-perl / snp_ details _ phase3 ?name = rs3024496&source = hapmap27 _ B36&tmpl = snp_ details _phase3 .
18.	Hunninghake G, Soto-Quiros M, Lasky-Su J, et al. Dust mite exposure modifies the effect of functional IL10 polymorphisms on allergy and asthma exacerbations. J Allergy Clin Immunol, 2008 ,122: 91-98.

1. Becklake MR, Ernst P. Environmental factors. Lancet, 1997 , 350 Suppl 2 : SII10 -13.
2. Newman-Taylor A. Environmental determinants of asthma. Lancet,1995, 345: 296-299.
3. Akdis CA, Joss A, Akdis M, et al. Mechanism of IL-10-induced T cell inactivation in allergic inflammation and normal response to allergens. Int Arch Allergy Immunol, 2001, 124: 180-182.
4. Palmer LJ, Celedón JC, Chapman HA, et al. Genome-wide linkage analysis of bronchodilator responsiveness and post-bronchodilator spirometric phenotypes in chronic obstructive pulmonary disease.Hum Mol Genet, 2003 , 12: 1199-1210.
5. Eskdale J, Gallagher G, Verweij CL, et al. Interleukin 10 secretion in relation to human IL-10 locus haplotypes. Proc Natl Acad Sci USA, 1998, 95: 9465-9470.
6. Rosenwasser LJ, Borish L. Genetics of atopy and asthma: the rationale behind promoter-based candidate gene studies ( IL-4 and IL-10) . Am J Respir Crit Care Med, 1997, 156: S152-S155.
7. Lim S, Crawley E, Woo P, et al. Haplotype associated with low interleukin-10 production in patients with severe asthma. Lancet,1998, 352 : 113.
8. 張嘉琳, 陳虹, 胡良平, 等. 白細胞介素4 和10 基因多態性與兒童哮喘的相關性及對細胞因子表達的影響. 中華醫學雜志,2002, 82: 114-118 .
9. Jurinke C, van den Boom D, Cantor CR, et al. Automated genotyping using the DNA MassArray technology. Methods Mol Biol, 2001 , 170: 103-116.
10. Leushner J, Chiu NH. Automated mass spectrometry: a revolutionary technology for clinical diagnostics. Mol Diagn, 2000 ,5 : 341-348.
11. Lyon H, Lange C, Lake S, et al. IL-10 gene polymorphisms are associated with asthma phenotypes in children. Genet Epidemiol,2004 , 26 : 155-165 .
12. Hang LW, Hsia TC, Chen WC, et al. Interleukin-10 gene -627 allele variants, not interleukin-I beta gene and receptor antagonist gene polymorphisms, are associated with atopic bronchial asthma. J Clin Lab Anal, 2003, 17 : 168-173.
13. Karjalainen J, Hulkkonen J, Nieminen MM, et al. Interleukin-10 gene promoter region polymorphism is associated with eosinophil count and circulating Immunoglobulin E in adult asthma. Clin Exp Allergy, 2003, 33: 78-83 .
14. Chatterjee R, Batra J, Kumar A, et al. Interleukin-10 promoter polymorphisms and atopic asthma in North Indians. Clin Exp Allergy, 2005, 35: 914-919.
15. Hobbs K, Negri J, KlinnertM, et al. Interleukin-10 and transforming growth factor-beta promoter polymorphisms in allergies and asthma.Am J Respir Crit Care Med, 1998 , 158: 1958 -1962 .
16. http: / /hapmap. ncbi. nlm. nih. gov/ cgi-perl / snp_ details _ phase3 ?name = rs1800896&source = hapmap27 _ B36&tmpl = snp_ details _phase3 .
17. http: / /hapmap. ncbi. nlm. nih. gov/ cgi-perl / snp_ details _ phase3 ?name = rs3024496&source = hapmap27 _ B36&tmpl = snp_ details _phase3 .
18. Hunninghake G, Soto-Quiros M, Lasky-Su J, et al. Dust mite exposure modifies the effect of functional IL10 polymorphisms on allergy and asthma exacerbations. J Allergy Clin Immunol, 2008 ,122: 91-98.

《中國呼吸與危重監護雜志》

白細胞介素10 基因單核苷酸多態性與哮喘遺傳易感性的相關性研究

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《中國呼吸與危重監護雜志》

白細胞介素10 基因單核苷酸多態性與哮喘遺傳易感性的相關性研究

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