A multi-centre study of candidate genes for wheeze and allergy: the International Study of Asthma and Allergies in Childhood Phase 2

被引：44

作者：

Genuneit, J. ^{[1
]}

Cantelmo, J. L. ^{[2
]}

Weinmayr, G. ^{[1
]}

Wong, G. W. K. ^{[3
]}

Cooper, P. J. ^{[4
]}

Riikjaerv, M. -A. ^{[5
]}

Gotua, M. ^{[6
]}

Kabesch, M. ^{[7
]}

von Mutius, E. ^{[8
]}

Forastiere, F. ^{[9
]}

Crane, J. ^{[10
]}

Nystad, W. ^{[11
]}

El-Sharif, N. ^{[12
]}

Batlles-Garrido, J. ^{[13
]}

Garcia-Marcos, L. ^{[14
,15
,16
]}

Garcia-Hernandez, G. ^{[17
]}

Morales-Suarez-Varela, M. ^{[18
,19
]}

Nilsson, L. ^{[20
]}

Braback, L. ^{[21
]}

Saraclar, Y. ^{[22
]}

Weiland, S. K. ^{[1
]}

Cookson, W. O. C. ^{[2
]}

Strachan, D. ^{[23
]}

Moffatt, M. F. ^{[2
]}

机构：

[1] Univ Ulm, Inst Epidemiol, D-89081 Ulm, Germany

[2] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England

[3] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Paediat, Shatin, Hong Kong, Peoples R China

[4] Ctr Invest FEPIS, Quininde, Ecuador

[5] Tallinn Childrens Hosp, Tallinn, Estonia

[6] Ctr Allergy & Immunol, Tbilisi, Georgia

[7] Hannover Med Sch, Ctr Paediat, Clin Pneumol & Neonatol, D-3000 Hannover, Germany

[8] Univ Munich, Dr von Haunersches Kinderspital, Munich, Germany

[9] Local Hlth Author Rome, Dept Epidemiol, Rome, Italy

[10] Wellington Sch Med & Hlth Sci, Wellington Asthma Res Grp, Wellington, New Zealand

[11] Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway

[12] AL Quds Univ, Fac Publ Hlth, Jerusalem, Israel

[13] Torrecardenas Hosp, Pediat Pulmonol Unit, Almeria, Spain

[14] Arrixaca Univ, Childrens Hosp, Pediat Allergy Unit, Murcia, Spain

[15] Arrixaca Univ, Childrens Hosp, Pulmonol Unit, Murcia, Spain

[16] CIBER Epidemiol & Publ Hlth CIBERESP, Murcia, Spain

[17] 12 Octubre Childrens Hosp, Pediat Allergy & Pneumol Unit, Madrid, Spain

[18] Univ Valencia, Dept Prevent Med & Publ Hlth, CIBER Epidemiol & Publ Hlth CIBERESP, Valencia, Spain

[19] Univ Valencia, Fdn Invest, Dr Peset Univ Hosp, Valencia, Spain

[20] Linkoping Univ Hosp, Fac Hlth Sci, Allergy Ctr, S-58185 Linkoping, Sweden

[21] Sundsvall Hosp, Dept Publ Hlth & Res, Sundsvall, Sweden

[22] Hacettepe Univ, Fac Med, Dept Pediat Allergy & Asthma, TR-06100 Ankara, Turkey

[23] Univ London, London, England

来源：

CLINICAL AND EXPERIMENTAL ALLERGY | 2009年 / 39卷 / 12期

基金：

英国惠康基金;

关键词：

allergy; asthma; candidate genes; multi-centre study; ATOPIC SENSITIZATION; POSITIONAL CLONING; RISK; POLYMORPHISMS; PREVALENCE; HAPLOTYPES; ECZEMA;

D O I：

10.1111/j.1365-2222.2009.03364.x

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

P>Background Common polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their associations with wheeze and allergy in a case-control sample from Phase 2 of the International Study of Asthma and Allergies in Childhood. Methods We compared 1105 wheezing and 3137 non-wheezing children aged 8-12 years from 17 study centres in 13 countries. Genotyping of 55 candidate single nucleotide polymorphisms (SNPs) in 14 genes was performed using the Sequenom System. Logistic regression models were fitted separately for each centre and each SNP. A combined per allele odds ratio and measures of heterogeneity between centres were derived by random effects meta-analysis. Results Significant associations with wheeze in the past year were detected in only four genes (IL4R, TLR4, MS4A2, TLR9, P < 0.05), with per allele odds ratios generally < 1.3. Variants in IL4R and TLR4 were also related to allergen-specific IgE, while polymorphisms in FCER1B (MS4A2) and TLR9 were not. There were also highly significant associations (P < 0.001) between SPINK5 variants and visible eczema (but not IgE levels) and between IL13 variants and total IgE. Heterogeneity of effects across centres was rare, despite differences in allele frequencies. Conclusions Despite the biological plausibility of IgE-related mechanisms in asthma, very few of the tested candidates showed evidence of association with both wheeze and increased IgE levels. We were unable to confirm associations of the positional candidates DPP10 and PHF11 with wheeze, although our study had ample power to detect the expected associations of IL13 variants with IgE and SPINK5 variants with eczema.

引用

页码：1875 / 1888

页数：14

共 28 条

[1] Positional cloning of a novel gene influencing asthma from Chromosome 2q14 [J].