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Tumour necrosis factor (TNF)-alpha is associated with childhood wheezing. A genetic predisposition to increased TNF-alpha production, influenced by single nucleotide gene polymorphisms, may be important. Frequencies of TNF-alpha-308G/A and lymphotoxin (LT)-alpha+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-alpha-308 and LT-alpha+252 polymorphisms were significantly different from controls. Haplotype analysis showed that TNF-alpha-308G, LT-alpha+252A/TNF-alpha-308A, LT-alpha+252A was associated with a markedly increased risk for both asthma and infant wheezing. The TNF-alpha-308G, LT-alpha+252G/TNF-alpha-308G, LT-alpha+252A combination was protective for asthma and infant wheezing. These findings were confirmed by analysis of Caucasian data. Nasal TNF-alpha levels were measured in the infants during acute wheezing episodes and higher, but nonsignificant levels were produced in those with one or two LT-alpha+252A alleles. Unexpectedly, significantly lower nasal TNF-alpha levels were found in the presence of one or two TNF-alpha-308A alleles. TNF-alpha-308/LT-alpha+252 genotype combinations had a significant influence on nasal TNF-alpha 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.
Bilolikar et al. (Sat,) studied this question.