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TNF Genotype May Play a Role in Asthma Susceptibility

The TNF-308 GG genotype appears to protect against the disease

TUESDAY, April 25 (HealthDay News) -- A genetic variant that alters the expression of tumor necrosis factor (TNF) may protect against asthma through its role in mediating inflammatory responses to air pollutants, according to a study published in the May issue of the American Journal of Respiratory and Critical Care Medicine.

Frank Gilliland, M.D., Ph.D., of the Keck School of Medicine at the University of Southern California in Los Angeles, and colleagues studied 3,699 children enrolled in the Children's Health Study. They examined the relationships between community ozone and polymorphisms in the TNF promoter gene, G-308A. They also looked at polymorphisms in two oxidant defense genes, GSTM1 and GSTP1.

Children who had the TNF-308 GG genotype had a 20 percent lower risk of asthma and lifetime wheezing compared to those who did not. The protective effect of the polymorphism was reduced in high-ozone communities, particularly in patients who had GSTM1 null and GSTP1 105 lle/Val (A105G) variants compared with other polymorphisms in the oxidant defense genes.

"Although we did not directly study the mechanisms for the effects of the TNF-308 GG variant or the effects of ozone exposure on TNF-mediated asthma and wheezing in children, we speculate that TNF-308 GG promoter genotype is associated with less intense inflammatory responses to oxidant stressors and that this reduced responsiveness results in reduced risk for asthma and wheezing," the authors conclude.

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