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


OBJECTIVE
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.
Wu
Hao
H
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.
Romieu
Isabelle
I
Sienra-Monge
Juan-Jose
JJ
del Rio-Navarro
Blanca Estela
BE
Anderson
Daniel M
DM
Dunn
Erin W
EW
Steiner
Lori L
LL
Lara-Sanchez
Irma del Carmen
Idel C
London
Stephanie J
SJ
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000453:epidemiology* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004781:Environmental Exposure; D005260:Female; D005838:Genotype; D006801:Humans; D006969:Hypersensitivity, Immediate; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008800:Mexico / Q000453:epidemiology; D010126:Ozone; D010287:Parent-Child Relations; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D008233:Lymphotoxin-alpha; D014028:Tobacco Smoke Pollution; D014409:Tumor Necrosis Factor-alpha; D010126:Ozone