Association of Single Nucleotide Polymorphisms in Interleukin-10 Gene with Asthma_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

YANG Xuexi ¹ , LI Fenxia ¹ , LI Xin ¹ , SUN Jingzhe ¹ , SUN Minying ¹ ,  LI Ming ^1,2

School of Biotechnology, Southern Medical University. Guangzhou, Guangdong,510515, ChinaCorresponding Author: LI Ming, E-mail:mingli1958@ 126. com;

Corresponding author：

LI Ming, Email: mingli1958@126.com

Keywords：

Interleukin-10; Single nucleotide polymorphisms; Asthma

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Objective To explore whether interleukin-10 ( IL-10 ) gene single nucleotide polymorphisms are associated with asthma. Methods The frequency of three single nucleotide polymorphisms ( rs1800896, rs3024492, and rs3024496) and haplotypes of IL-10 gene were analysed in 302 adult asthmatic subjects and 275 controls of Han Chinese in Guangzhou using MALDI-TOF-MS and MassARRAY-IPLEX. The genotype and allele frequencies were analyzed by Chi-square test in both groups.
Logistic regression analysis with adjustment for age and sex was conducted. Odds ratio ( OR) and 95%confidence interval ( 95% CI) were calculated to analyze the associations between the susceptibility of asthma and genotypes. Results ①Three genotypes GG, GA, and AA of rs1800896 were found in Han Chinese in
Guangzhou. The frequencies of GG, GA, and AA genotypes were 2. 12% , 39. 65% , and 58. 23% ,respectively. The relative risk of developing asthma in the carriers of GA was significantly higher than that in the carriers of AA ( OR=4. 827, P lt;0. 001) . ②Two genotypes AA and AT of rs3024492 were found in Han Chinese in Guangzhou. The frequencies of AA and AT genotypes were 1. 22% and 98. 78% , respectively.The rs3024492 polymorphism was not related to susceptibility in asthma. ③Two genotypes TT and CT of rs3024496 were found in Han Chinese in Guangzhou. The frequencies of TT and CT genotypes were 90. 59% and 9. 41% , respectively. The rs3024496 polymorphism was not related to susceptibility in asthma. Conclusion In IL-10 gene single nucleotide polymorphisms, rs1800896 but not rs3024492 and rs3024496 is
statistically related with the development of asthma.

Citation： YANG Xuexi,LI Fenxia,LI Xin,SUN Jingzhe,SUN Minying,LI Ming. Association of Single Nucleotide Polymorphisms in Interleukin-10 Gene with Asthma. Chinese Journal of Respiratory and Critical Care Medicine, 2010, 9(5): 485-489. doi: Copy

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.	张嘉琳, 陈虹, 胡良平, 等. 白细胞介素4 和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, 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. 张嘉琳, 陈虹, 胡良平, 等. 白细胞介素4 和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, 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.

Chinese Journal of Respiratory and Critical Care Medicine

Association of Single Nucleotide Polymorphisms in Interleukin-10 Gene with Asthma

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