Combined effect of tumour necrosis factor-α and interleukin-13 polymorphisms on bronchial hyperresponsiveness in Korean children with asthma

被引：30

作者：

Kim, H-B. ^{[2
]}

Kang, M-J. ^{[3
]}

Lee, S-Y. ^{[4
]}

Jin, H-S. ^{[1
]}

Kim, J-H. ^{[1
]}

Kim, B-S. ^{[1
]}

Jang, S-O. ^{[3
]}

Lee, Y-C. ^{[5
,6
]}

Sohn, M-H. ^{[7
,8
]}

Kim, K-E. ^{[7
,8
]}

Hong, S-J. ^{[1
]}

机构：

[1] Univ Ulsan, Coll Med, Asan Med Ctr, Div Allergy & Resp Med,Dept Pediat, Seoul 138736, South Korea

[2] Inje Univ, Sanggye Paik Hosp, Dept Pediat, Seoul, South Korea

[3] Univ Ulsan, Coll Med, Asan Inst Life Sci, Seoul, South Korea

[4] Hallym Univ, Coll Med, Hangang Sacred Heart Hosp, Dept Pediat, Seoul, South Korea

[5] Chonbuk Natl Univ, Sch Med, Dept Internal Med, Jeonju, South Korea

[6] Chonbuk Natl Univ, Sch Med, Res Ctr Allerg Immune Dis, Jeonju, South Korea

[7] Yonsei Univ, Coll Med, Dept Pediat, Severance Childrens Hosp, Seoul, South Korea

[8] Yonsei Univ, Coll Med, Severance Childrens Hosp, Inst Allergy, Seoul, South Korea

来源：

CLINICAL AND EXPERIMENTAL ALLERGY | 2008年 / 38卷 / 05期

关键词：

asthma; bronchial hyperresponsiveness; combined effect; IL-13; TNF-alpha;

D O I：

10.1111/j.1365-2222.2008.02965.x

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

Background TNF-alpha and IL-13, two pivotal pro-inflammatory cytokines, are increased in asthmatic airways and may be linked to asthma susceptibility and/or bronchial hyperresponsiveness (BHR). Objective We investigated the association between the TNF-alpha - 308G/A polymorphism and asthma susceptibility or asthma-related phenotypes in Korean children with asthma, and tested for a combined effect with IL-13 polymorphisms. Methods Asthmatic children (n = 719) and non-atopic healthy control children (n = 243) were evaluated for asthma phenotypes including total serum IgE and BHR to methacholine. Genotypes were determined by PCR-restriction fragment length polymorphism analysis. Results The allele frequency of TNF-alpha - 308A in asthmatics (14.1%) was higher than that in control children [8.7%, odds ratio (OR) 1.72, 95% confidence interval (CI) 1.05-2.82]. Significantly lower PC20 values were found in asthmatic children carrying one or two copies of the TNF-a risk allele (- 308A) vs. those homozygous for the common allele (P = 0.026). Combined analysis revealed that atopic asthmatic children co-inherited the risk alleles of TNF-alpha - 308G/A and IL-13 + 2044G/A more frequently than control children (aOR 1.91, 95% CI 1.00-3.65), and asthmatic children co-inheriting both risk alleles had significantly lower PC20 values vs. asthmatic children homozygous for the common alleles (P = 0.024). Conclusion The TNF-alpha promoter polymorphism (- 308G/A) may be associated with asthma susceptibility and BHR in Korean children with asthma. In addition, there appears to be a synergistic effect between the TNF-alpha promoter polymorphism and an IL-13 coding region polymorphism in terms of asthma susceptibility and BHR in this population.

引用

页码：774 / 780

页数：7

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