Joint effect of obesity and TNFA variability on asthma: two international cohort studies

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), Barcelona, 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), Barcelona, 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, Zurich, Switzerland; and Institute of Medical Genetics, Division of Medical Molecular Genetics and Gene Diagnostics, University of Zurich, Zurich, Switzerland
⁴ CIBER Epidemiologia y Salud Pública (CIBERESP), Barcelona, Spain; and Genes and Disease Program, Center for Genomic Regulation, Barcelona, Spain
⁵ Respiratory Epidemiology and Public Health Group, National Heart and Lung Institute, Imperial College, London, United Kingdom
⁶ Institutes of Social and Preventive Medicine & Surgical Pathology, Molecular Epidemiology/Cancer Registry, University of Zurich & University Hospital Zurich, Zurich, Switzerland
⁷ Institute of Medical Genetics, Division of Medical Molecular Genetics and Gene Diagnostics, University of Zurich, Zurich, Switzerland
⁸ Dept of Respiratory Medicine, University Hospital, Umeå, Sweden
⁹ Institute of Epidemiology, Helmholtz Centre, Munich, Germany
¹⁰ Dept of Medical Sciences: Respiratory Medicine and Allergology Uppsala University, Uppsala, Sweden
¹¹ Haukeland University Hospital Bergen, Bergen, Norway
¹² Inserm, U823, Centre de Recherche Albert Bonniot, Immunobiologie et Immunothérapie des cancers, La Tronche, F-38706 France; University Joseph Fourier, Grenoble, F-38041 France; and Centre Hospitalier Universitaire de Grenoble, Grenoble, F-38043 France
¹³ Division of Pulmonary Medicine, University Hospitals of Geneva, Geneva, Switzerland
¹⁴ 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), Barcelona, Spain; and Universitat Pompeu Fabra, Barcelona, Spain
¹⁵ German Research Center for Environmental Health, Helmholtz Centre GSF, Munich, Germany
¹⁶ CIBER Epidemiologia y Salud Pública (CIBERESP), Barcelona, Spain; Genes and Disease Program, Center for Genomic Regulation, Barcelona, Spain; and Universitat Pompeu Fabra, Barcelona, Spain

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

	Abstract

Obesity is a risk factor for asthma. Adipose tissue expresses proinflammatory molecules including tumour necrosis factor (TNF), and levels of TNF are also related to polymorphisms in the TNFA gene. We examined the joint effect of obesity and TNFA variability on asthma in adults by combining two population-based studies.

The European Community Respiratory Health Survey (ECRHS) and the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults (SAPALDIA) used comparable protocols, questionnaires and measures of lung function and atopy. DNA samples from 9, 167 participants were genotyped for TNFA-308 and LTA+252 gene variants.

Obesity and TNFA were associated with asthma when mutually adjusting for their independent effects (Odds Ratio (OR) for obesity=2.4, 95%CI 1.7–3.2; OR for TNFA-308 polymorphism=1.3, 95%CI 1.1–1.6). The association of obesity with asthma was stronger for subjects carrying the G/A and A/A TNFA-308 genotypes compared to the more common G/G genotype, particularly among non-atopics (OR for G/A and A/A genotypes=6.1, 95%CI 2.5–14.4; OR for G/G genotype=1.7, 95%CI 0.8–3.3; p-value for interaction <0.05).

These findings provide for the first time evidence for a complex pattern of interaction between obesity, a proinflammatory genetic factor and asthma.