Joint effect of obesity and TNFA variability on asthma: two international cohort studies.
Francesc Castro-Giner
(1, 2, 3)
,
Manolis Kogevinas
(1, 3, 4, 5)
,
Medea Imboden
(6, 7)
,
Rafael de Cid
(3, 8)
,
Deborah Jarvis
(9)
,
Martin Mächler
(6)
,
Wolfgang Berger
(7)
,
Peter G. Burney
(9)
,
Karl A. Franklin
(10)
,
Juan R. Gonzalez
(1, 2, 3, 11)
,
Joachim Heinrich
(12)
,
Christer Janson
(13)
,
Ernst Reidar Omenaas
(14)
,
Isabelle Pin
(15)
,
Thierry Rochat
(16)
,
Jordi Sunyer
(1, 2, 3)
,
Matthias Wjst
(12)
,
Josep-Maria Antó
(1, 2, 3)
,
Xavier Estivill
(3, 17)
,
Nicole M. Probst-Hensch
(6)
1
CREAL -
Center for Research in Environmental Epidemiology
2 IMIM-Hospital del Mar
3 CIBERESP - CIBER Epidemiologia y Salud Pública
4 Medical School, University of Crete, Heraklion, Greece
5 CIBER Epidemiologia y Salud Pública (CIBERESP), Barcelona
6 Institutes of Social and Preventive Medicine & Surgical Pathology, Molecular Epidemiology/Cancer Registry
7 Institute of Medical Genetics, Division of Medical Molecular Genetics and Gene Diagnostics
8 Genes and Disease Program, Center for Genomic Regulation
9 Respiratory Epidemiology and Public Health Group, National Heart and Lung Institute, Imperial College
10 Department of Respiratory Medicine
11 Genes & Disease Program, Biostatistics Unit
12 EPI - Institute of Epidemiology [Neuherberg]
13 Dept of Medical Sciences, Respiratory Medicine and Allergology
14 Haukeland University Hospital
15 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
16 Division of Pulmonary Medicine
17 UPF - Universitat Pompeu Fabra [Barcelona]
2 IMIM-Hospital del Mar
3 CIBERESP - CIBER Epidemiologia y Salud Pública
4 Medical School, University of Crete, Heraklion, Greece
5 CIBER Epidemiologia y Salud Pública (CIBERESP), Barcelona
6 Institutes of Social and Preventive Medicine & Surgical Pathology, Molecular Epidemiology/Cancer Registry
7 Institute of Medical Genetics, Division of Medical Molecular Genetics and Gene Diagnostics
8 Genes and Disease Program, Center for Genomic Regulation
9 Respiratory Epidemiology and Public Health Group, National Heart and Lung Institute, Imperial College
10 Department of Respiratory Medicine
11 Genes & Disease Program, Biostatistics Unit
12 EPI - Institute of Epidemiology [Neuherberg]
13 Dept of Medical Sciences, Respiratory Medicine and Allergology
14 Haukeland University Hospital
15 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
16 Division of Pulmonary Medicine
17 UPF - Universitat Pompeu Fabra [Barcelona]
Manolis Kogevinas
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Christer Janson
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- ORCID : 0000-0001-5093-6980
Isabelle Pin
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- ORCID : 0000-0002-7529-6999
Résumé
Obesity is a risk factor for asthma. Adipose tissue expresses pro-inflammatory molecules including tumour necrosis factor (TNF), and levels of TNF are also related to polymorphisms in the TNF-alpha (TNFA) gene. The current authors 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 and the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults used comparable protocols, questionnaires and measures of lung function and atopy. DNA samples from 9,167 participants were genotyped for TNFA -308 and lymphotoxin-alpha (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% confidence interval (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 with the more common G/G genotype, particularly among nonatopics (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). The present findings provide, for the first time, evidence for a complex pattern of interaction between obesity, a pro-inflammatory genetic factor and asthma.