TNFA-308 in Two International Population-Based Cohorts Shows Increased Risk for Asthma

¹ Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain; and CIBER Epidemiologia y Salud Pública (CIBERESP), Spain
² Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain; CIBER Epidemiologia y Salud Pública (CIBERESP), Spain; and Medical School, University of Crete, Heraklion, Greece
³ Institutes of Social and Preventive Medicine & Surgical Pathology, Molecular Epidemiology/Cancer Registry, University of Zurich & University Hospital Zurich, Switzerland
⁴ CIBER Epidemiologia y Salud Pública (CIBERESP), Spain; and Genes and Disease Program, Center for Genomic Regulation, Barcelona National Genotyping Center
⁵ Dept of Applied Mathematics and Computer Science, Ghent, Belgium; Ghent University Hospital, Ghent, Belgium; and StepGen CVBA, Merelbeke, Belgium
⁶ Institutes of Social and Preventive Medicine & Surgical Pathology, Molecular Epidemiology/Cancer Registry, University of Zurich & University Hospital Zurich, Switzerland; and Institute of Medical Genetics, Division of Medical Molecular Genetics and Gene Diagnostics, University of Zurich, Switzerland
⁷ Institute of Social and Preventive Medicine, University of Basel, Switzerland
⁸ Institute of Medical Genetics, Division of Medical Molecular Genetics and Gene Diagnostics, University of Zurich, Switzerland
⁹ Dept of Medical Sciences: Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden
¹⁰ Respiratory Epidemiology and Public Health Group, National Heart and Lung Institute, Imperial College, London, United Kingdom
¹¹ Division of Pulmonary Medicine, University Hospitals of Geneva, Geneva, Switzerland
¹² CIBER Epidemiologia y Salud Pública (CIBERESP), Spain; Genes and Disease Program, Center for Genomic Regulation, Barcelona National Genotyping Center; and Universitat Pompeu Fabra, Barcelona, Spain
¹³ Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain; CIBER Epidemiologia y Salud Pública (CIBERESP), Spain; and Universitat Pompeu Fabra, Barcelona, Spain
¹⁴ GSF Forschungszentrum für Umwelt und Gesundheit, Institut für Epidemiologie, Neuherberg, München, Germany

^* To whom correspondence should be addressed. E-mail: kogevinas{at}imim.es.

	Abstract

Genetic association studies have related the Tumour Necrosis Factor alpha (TNFA) -308 G/A polymorphism with increased risk to asthma but results are inconsistent.

To test whether two single nucleotide polymorphisms of the TNFA and lymphotoxin alpha (LTA) genes are associated with asthma, bronchial hyper-responsiveness and atopy in adults, by combining the results from two large population-based multicenter studies and to conduct a meta-analysis of previously published studies.

The European Community Respiratory Health Survey (ECRHS) and the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults (SAPALDIA) have used comparable protocols including questionnaires for respiratory symptoms and measures of lung function and atopy. DNA samples from 11,136 participants were genotyped for TNFA-308 and LTA+252. Logistic regression with fixed and random effects models and non-parametric techniques were used.

The prevalence of asthma was 6%. The TNFA-308 polymorphism was associated with increased asthma prevalence (odds ratio for the A allele=1.3, 95%CI 1.1–1.5) and with bronchial hyper-responsiveness (OR=1.2, 95%CI 1.0–1.3). No consistent association was found for atopy. The LTA+252 polymorphism was not associated with any of the outcomes. A meta-analysis of 17 studies showed an increased asthma risk of the TNFA-308 A allele (OR=1.3, 95%CI 1.2–1.5).

The TNFA-308 polymorphism is associated with a moderately increased risk for asthma and bronchial hyper-responsiveness, but not with atopy. These results are supported by a meta-analysis of previously published studies.