Parental Smoking Modifies the Relation between Genetic Variation in Tumor Necrosis Factor-α (TNF) and Childhood Asthma
National Institute of Environmental Health Sciences -- Environmental Health Perspectives
DOI 10.1289/ehp.9740
Keyword(s)
  1. allergy
  2. asthma
  3. atopy
  4. environmental tobacco smoke
  5. genetic predisposition to disease
  6. lymphotoxin-α (LTA)
  7. ozone
  8. secondhand smoke
  9. single nucleotide polymorphism (SNP)
  10. tumor necrosis factor-α (TNF)
Abstract(s)

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.