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

共 32 条

[1] Signalling pathways of the TNF superfamily: A double-edged sword [J].

Aggarwal, BB .

NATURE REVIEWS IMMUNOLOGY, 2003, 3 (09) :745-756

[2] Activation of tumor necrosis factor receptor 1 in airway smooth muscle: A potential pathway that modulates bronchial hyper-responsiveness in asthma? [J].

Amrani Y. ;

Chen H. ;

Panettieri Jr. R.A. .

Respiratory Research, 2000, 1 (1) :49-53

[3]

[Anonymous], 1987, AM REV RESPIR DIS, V136, P225

[4]

Bucková D, 2002, J INVEST ALLERG CLIN, V12, P192

[5] STANDARDIZATION OF BRONCHIAL INHALATION CHALLENGE PROCEDURES [J].

CHAI, H ;

FARR, RS ;

FROEHLICH, LA ;

MATHISON, DA ;

MCLEAN, JA ;

ROSENTHAL, RR ;

SHEFFER, AL ;

SPECTOR, SL ;

TOWNLEY, RG .

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1975, 56 (04) :323-327

[6] A genome-wide search for quantitative trait loci underlying asthma [J].

Daniels, SE ;

Bhattacharrya, S ;

James, A ;

Leaves, NI ;

Young, A ;

Hill, MR ;

Faux, JA ;

Ryan, GF ;

leSouef, PN ;

Lathrop, GM ;

Musk, AW ;

Cookson, WOCM .

NATURE, 1996, 383 (6597) :247-250

[7] Lack of association between the tumor necrosis factor-α regulatory region genetic polymorphisms associated with elevated tumor necrosis factor-α levels and children with asthma [J].

El Bahlawan, L ;

Christensen, M ;

Binaei, S ;

Murphy, C ;

Zhang, Q ;

Quasney, M .

CHEST, 2003, 123 (03) :374S-375S

[8] A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children [J].

Graves, PE ;

Kabesch, M ;

Halonen, M ;

Holberg, CJ ;

Baldini, M ;

Fritzsch, C ;

Weiland, SK ;

Erickson, RP ;

von Mutius, E ;

Martinez, FD .

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2000, 105 (03) :506-513

[9] Requirement for IL-13 independently of IL-4 in experimental asthma [J].

Grünig, G ;

Warnock, M ;

Wakil, AE ;

Venkayya, R ;

Brombacher, F ;

Rennick, DM ;

Sheppard, D ;

Mohrs, M ;

Donaldson, DD ;

Locksley, RM ;

Corry, DB .

SCIENCE, 1998, 282 (5397) :2261-2263

[10] Genetic variants of IL-13 signalling and human asthma and atopy [J].

Heinzmann, A ;

Mao, XQ ;

Akaiwa, M ;

Kreomer, RT ;

Gao, PS ;

Ohshima, K ;

Umeshita, R ;

Abe, Y ;

Braun, S ;

Yamashita, T ;

Roberts, MH ;

Sugimoto, R ;

Arima, K ;

Arinobu, Y ;

Yu, B ;

Kruse, S ;

Enomoto, T ;

Dake, Y ;

Kawai, M ;

Shimazu, S ;

Sasaki, S ;

Adra, CN ;

Kitaichi, M ;

Inoue, H ;

Yamauchi, K ;

Tomichi, N ;

Kurimoto, F ;

Hamasaki, N ;

Hopkin, JM ;

Izuhara, K ;

Shirakawa, T ;

Deichmann, KA .

HUMAN MOLECULAR GENETICS, 2000, 9 (04) :549-559

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