Gene-environment interaction for childhood asthma and exposure to farming in Central Europe

被引：111

作者：

Ege, Markus J. ^{[1
]}

Strachan, David P. ^{[2
]}

Cookson, William O. C. M. ^{[3
]}

Moffatt, Miriam F. ^{[3
]}

Gut, Ivo ^{[4
]}

Lathrop, Mark ^{[4
,5
]}

Kabesch, Michael ^{[6
]}

Genuneit, Jon ^{[7
]}

Buechele, Gisela ^{[7
]}

Sozanska, Barbara ^{[8
]}

Boznanski, Andrzej ^{[8
]}

Cullinan, Paul ^{[3
]}

Horak, Elisabeth ^{[9
]}

Bieli, Christian ^{[10
,11
]}

Braun-Fahrlaender, Charlotte ^{[10
,11
]}

Heederik, Dick ^{[12
]}

von Mutius, Erika ^{[1
]}

机构：

[1] Univ Childrens Hosp Munich, Munich, Germany

[2] Univ London, Div Community Hlth Sci, London, England

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

[4] Ctr Natl Genotypage, Inst Genom, Evry, France

[5] Fdn Jean Dausset CEPH, Paris, France

[6] Hannover Med Sch, Clin Pediat Pneumol & Neonatol, D-3000 Hannover, Germany

[7] Univ Ulm, Inst Epidemiol, Ulm, Germany

[8] Wroclaw Med Univ, Dept Paediat Allergol & Cardiol 1, Wroclaw, Poland

[9] Innsbruck Med Univ, Div Cardiol & Pulmonol, Dept Pediat & Adolescents, Innsbruck, Austria

[10] Swiss Trop & Publ Hlth Inst, Basel, Switzerland

[11] Univ Basel, Basel, Switzerland

[12] Univ Utrecht, Inst Risk Assessment Sci, Div Environm Epidemiol, Utrecht, Netherlands

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2011年 / 127卷 / 01期

基金：

英国惠康基金;

关键词：

Childhood asthma; atopy; GWAS; gene-by-environment interaction; candidate genes; GENOMEWIDE ASSOCIATION; GLUTAMATE; CHILDREN;

D O I：

10.1016/j.jaci.2010.09.041

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

Background: Asthma is a disease in which both genetic and environmental factors play important roles. The farming environment has consistently been associated with protection from childhood asthma and atopy, and interactions have been reported with polymorphisms in innate immunity genes. Objective: To detect gene-environment interactions for asthma and atopy in the farming environment. Methods: We performed a genome-wide interaction analysis for asthma and atopy by using 500,000 genotyped single nucleotide polymorphisms (SNPs) and farm-related exposures in 1708 children from 4 rural regions of Central Europe. We also tested selectively for interactions between farm exposures and 7 SNPs that emerged as genome-wide significant in a large meta-analysis of childhood asthma and 5 SNPs that had been reported previously as interacting with farm exposures for asthma or atopy. Results: Neither the asthma-associated SNPs nor the SNPs previously published for interactions with asthma showed significant interactions. The genome-wide interaction study did not reveal any significant interactions with SNPs within genes in the range of interacting allele frequencies from 30% to 70%, for which our study was well powered. Among rarer SNPs, we identified 15 genes with strong interactions for asthma or atopy in relation to farming, contact with cows and straw, or consumption of raw farm milk. Conclusion: Common genetic polymorphisms are unlikely to moderate the protective influence of the farming environment on childhood asthma and atopy, but rarer variants, particularly of the glutamate receptor, metabotropic 1 gene, may do so. Given the limited statistical power of our study, these findings should be interpreted with caution before being replicated in independent farm populations. (J Allergy Clin Immunol 2011;127:138-44.)

引用

页码：138 / U226

页数：11

共 14 条

[11] Role of glutamate on T-cell mediated immunity [J].