Tumour necrosis factor gene polymorphisms and childhood wheezing.
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
H
H
Dept of Paediatric Respiratory Medicine, Royal BromptonHospital, Sydney Street, London SW3 6NP, UK.
Nam
A R
AR
Rosenthal
M
M
Davies
J C
JC
Henderson
D C
DC
Balfour-Lynn
I M
IM
D000293:Adolescent; D000367:Age Factors; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D017817:Nasal Lavage Fluid / Q000276:immunology; D011110:Polymorphism, Genetic; D012135:Respiratory Sounds / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology
D014409:Tumor Necrosis Factor-alpha