Parental Smoking Modifies the Relation between Genetic Variation in Tumor Necrosis Factor-α ( TNF ) and Childhood Asthma

Autor: Daniel M. Anderson, Hao Wu, Lori Steiner, Blanca Estela Del Río-Navarro, Erin W. Dunn, J. J. L. Sienra-Monge, Irma del Carmen Lara-Sanchez, Stephanie J. London, Isabelle Romieu
Rok vydání: 2007
Předmět:
Hypersensitivity
Immediate
Male
Allergy
Health
Toxicology and Mutagenesis
atopy
environmental tobacco smoke
Atopy
lymphotoxin-α (LTA)
0302 clinical medicine
Risk Factors
immune system diseases
tumor necrosis factor-α (TNF)
Medicine
Parent-Child Relations
Child
Lymphotoxin-alpha
0303 health sciences
Environmental exposure
3. Good health
Child
Preschool
Children's Health
Female
Tumor necrosis factor alpha
Adult
Lymphotoxin alpha
Adolescent
Genotype
Polymorphism
Single Nucleotide
Proinflammatory cytokine
03 medical and health sciences
Ozone
single nucleotide polymorphism (SNP)
Genetic variation
Humans
Mexico
030304 developmental biology
Asthma
genetic predisposition to disease
Tumor Necrosis Factor-alpha
business.industry
Research
Public Health
Environmental and Occupational Health
Environmental Exposure
asthma
allergy
medicine.disease
030228 respiratory system
Immunology
Tobacco Smoke Pollution
business
secondhand smoke
Zdroj: Environmental Health Perspectives
ISSN: 1552-9924
0091-6765
DOI: 10.1289/ehp.9740
Popis: Background Polymorphisms in the proinflammatory cytokine genes tumor necrosis factor-α (TNF) and lymphotoxin-α (LTA, also called TNF-β) have been associated with asthma and atopy in some studies. Parental smoking is a consistent risk factor for childhood asthma. Secondhand smoke and ozone both stimulate TNF production. Objectives Our goal was to investigate whether genetic variation in TNF and LTA is associated with asthma and atopy and whether the association is modified by parental smoking in a Mexican population with high ozone exposure. Methods We genotyped six tagging single nucleotide polymorphisms (SNPs) in TNF and LTA, including functional variants, in 596 nuclear families consisting of asthmatics 4–17 years of age and their parents in Mexico City. Atopy was determined by skin prick tests. Results The A allele of the TNF-308 SNP was associated with increased risk of asthma [relative risk (RR) = 1.54; 95% confidence interval (CI), 1.04–2.28], especially among children of non-smoking parents (RR = 2.06; 95% CI, 1.19–3.55; p for interaction = 0.09). Similarly, the A allele of the TNF-238 SNP was associated with increased asthma risk among children of nonsmoking parents (RR = 2.21; 95% CI, 1.14–4.30; p for interaction = 0.01). LTA SNPs were not associated with asthma. Haplotype analyses reflected the single SNP findings in magnitude and direction. TNF and LTA SNPs were not associated with the degree of atopy. Conclusions Our results suggest that genetic variation in TNF may contribute to childhood asthma and that associations may be modified by parental smoking.
Databáze: OpenAIRE
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