Journal
ENVIRONMENTAL HEALTH PERSPECTIVES
Volume 115, Issue 4, Pages 616-622Publisher
US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
DOI: 10.1289/ehp.9740
Keywords
allergy; asthma; atopy; environmental tobacco smoke; genetic predisposition to disease; lymphotoxin-alpha (LTA); ozone; secondhand smoke; single nucleotide polymorphism (SNP); tumor necrosis factor-alpha (TNF)
Funding
- Intramural NIH HHS [Z01 ES049019] Funding Source: Medline
- NIEHS NIH HHS [Z01 ES 49019] Funding Source: Medline
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BACKGROUND: Polymorphisms in the proinflammatory cytokine genes tumor necrosis factor-alpha (TNT) and. lymphotoxin-alpha (LTA, also called TNF-beta) 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 L TA 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 L TA, 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 nonsmoking parents (RR = 2.06, 95% Cl, 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% Cl, 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.
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