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Tumour necrosis factor gene polymorphisms and childhood wheezing

¹ Dept of Paediatric Respiratory Medicine, Royal Brompton Hospital, ² Dept of Paediatrics, and ³ Dept of Immunology, Chelsea & Westminster Hospital, and ⁴ Dept Clinical Immunology, Hammersmith Hospital, London, UK.

CORRESPONDENCE: I. M. Balfour-Lynn, Dept of Paediatric Respiratory Medicine, Royal Brompton & Harefield NHS Trust, Sydney Street, London SW3 6NP, UK. Fax: 44 2073518763. E-mail: i.balfourlynn{at}ic.ac.uk

Keywords: Asthma, genetics, paediatric, tumour necrosis factor-

Received: June 15, 2004
Accepted June 8, 2005

Tumour necrosis factor (TNF)- is associated with childhood wheezing. A genetic predisposition to increased TNF- production, influenced by single nucleotide gene polymorphisms, may be important.

Frequencies of TNF--308G/A and lymphotoxin (LT)-+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--308 and LT-+252 polymorphisms were significantly different from controls.

Haplotype analysis showed that TNF--308G, LT-+252A/TNF--308A, LT-+252A was associated with a markedly increased risk for both asthma and infant wheezing. The TNF--308G, LT-+252G/TNF--308G, LT-+252A combination was protective for asthma and infant wheezing. These findings were confirmed by analysis of Caucasian data. Nasal TNF- levels were measured in the infants during acute wheezing episodes and higher, but nonsignificant levels were produced in those with one or two LT-+252A alleles. Unexpectedly, significantly lower nasal TNF- levels were found in the presence of one or two TNF--308A alleles. TNF--308/LT-+252 genotype combinations had a significant influence on nasal TNF- 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.

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