Tumour necrosis factor gene polymorphisms and childhood wheezing

Abstract

Tumour necrosis factor (TNF)-α is associated with childhood wheezing. A genetic predisposition to increased TNF-α production, influenced by single nucleotide gene polymorphisms, may be important. Frequencies of TNF-α-308G/A and lymphotoxin (LT)-α+252G/A polymorphisms were compared in 115 asthmatic children, 55 wheezy infants and 156 control school children from the UK. Genotype frequencies for the TNF-α-308 and LT-α+252 polymorphisms were significantly different from controls. Haplotype analysis showed that TNF-α-308G, LT-α+252A/TNF-α-308A, LT-α+252A was associated with a markedly increased risk for both asthma and infant wheezing. The TNF-α-308G, LT-α+252G/TNF-α-308G, LT-α+252A combination was protective for asthma and infant wheezing. These findings were confirmed by analysis of Caucasian data. Nasal TNF-α levels were measured in the infants during acute wheezing episodes and higher, but nonsignificant levels were produced in those with one or two LT-α+252A alleles. Unexpectedly, significantly lower nasal TNF-α levels were found in the presence of one or two TNF-α-308A alleles. TNF-α-308/LT-α+252 genotype combinations had a significant influence on nasal TNF-α levels. In conclusion, these findings may have implications for future early intervention studies by helping to identify infants at increased risk for wheezing and childhood asthma. Copyright©ERS Journals Ltd 2005.