• 1 南方醫(yī)科大學(xué)生物技術(shù)學(xué)院抗體工程研究所( 廣東廣州 510515) ;;
  • 2 中山大學(xué)達(dá)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(guān)計劃( 編號: 2008A1-E4151);

目的  探討白細(xì)胞介素10 ( IL-10) 基因三個單核苷酸多態(tài)性位點( rs1800896、rs3024496 和rs3024492) 與哮喘遺傳易感性的相關(guān)性。方法  應(yīng)用基質(zhì)輔助激光解吸附電離飛行時間質(zhì)譜( MALDI-TOF-MS) 平臺及MassARRAY-IPLEX 技術(shù), 分別對廣州地區(qū)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(tài)性位點( rs1800896、rs3024496 和rs3024492) 進(jìn)行基因分型并分析兩組間分布情況。用Χ2 檢驗統(tǒng)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(shù)比( OR) 和95% 可信區(qū)間( CI) , 評價多態(tài)性位點與哮喘遺傳易感性的相關(guān)性。結(jié)果  ① rs1800896 位點在廣州地區(qū)漢族人群中存在GG、GA、AA 三種多態(tài)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(qū)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(tài)性與哮喘的易感性無關(guān)。③rs3024496 位點在廣州地區(qū)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(tài)性與哮喘的易感性無關(guān)。結(jié)論  在IL-10 三個單核苷酸多態(tài)性位點中, rs1800896 與哮喘的易感性顯著相關(guān), 而rs3024492 和rs3024496 與哮喘的易感性不相關(guān)

引用本文： 楊學(xué)習(xí),李粉霞,李欣,孫靜哲,孫敏英,李明. 白細(xì)胞介素10 基因單核苷酸多態(tài)性與哮喘遺傳易感性的相關(guān)性研究. 中國呼吸與危重監(jiān)護(hù)雜志, 2010, 9(5): 485-489. doi: 復(fù)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(xì)胞介素4 和10 基因多態(tài)性與兒童哮喘的相關(guān)性及對細(xì)胞因子表達(dá)的影響. 中華醫(yī)學(xué)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. 1. Becklake MR, Ernst P. Environmental factors. Lancet, 1997 , 350 Suppl 2 : SII10 -13.
  2. 2. Newman-Taylor A. Environmental determinants of asthma. Lancet,1995, 345: 296-299.
  3. 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. 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. 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. 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. 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. 8. 張嘉琳, 陳虹, 胡良平, 等. 白細(xì)胞介素4 和10 基因多態(tài)性與兒童哮喘的相關(guān)性及對細(xì)胞因子表達(dá)的影響. 中華醫(yī)學(xué)雜志,2002, 82: 114-118 .
  9. 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. 10. Leushner J, Chiu NH. Automated mass spectrometry: a revolutionary technology for clinical diagnostics. Mol Diagn, 2000 ,5 : 341-348.
  11. 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. 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. 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. 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. 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. 16. http: / /hapmap. ncbi. nlm. nih. gov/ cgi-perl / snp_ details _ phase3 ?name = rs1800896&source = hapmap27 _ B36&tmpl = snp_ details _phase3 .
  17. 17. http: / /hapmap. ncbi. nlm. nih. gov/ cgi-perl / snp_ details _ phase3 ?name = rs3024496&source = hapmap27 _ B36&tmpl = snp_ details _phase3 .
  18. 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.