Format

Send to

Choose Destination
Environ Health Perspect. 2007 Apr;115(4):616-22. Epub 2007 Jan 16.

Parental smoking modifies the relation between genetic variation in tumor necrosis factor-alpha (TNF) and childhood asthma.

Author information

1
Laboratory of Respiratory Biology, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health/DHHS, Research Triangle Park, NC 27709, USA.

Abstract

BACKGROUND:

Polymorphisms in the proinflammatory cytokine genes tumor necrosis factor-alpha (TNF) 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 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.

PMID:
17450233
PMCID:
PMC1852663
DOI:
10.1289/ehp.9740
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center