Tumour necrosis factor (TNF) is a proinflammatory cytokine that increases h
uman airway tissue responsiveness and is considered a candidate gene for as
thma. Two common polymorphisms (LT alpha NcoI and TNF alpha-308) in the TNF
gene complex were studied in 600 subjects from 131 Italian families with a
topic asthmatic children. Skin prick test (SPT), total IgE levels, atopy (d
efined as increased IgE levels or SPT positivity or both), bronchial hyperr
esponsiveness, and clinical asthma were investigated. The observed distribu
tion of the identical by descent alleles at the LT alpha NcoI locus was dif
ferent from expected for SPT and atopy (p=0.015). The LT alpha NcoI genotyp
e distribution for increased IgE levels was different between males and fem
ales (p=0.0011), and an association of the 2.2 genotype with increased IgE
levels was observed in females (p=0.0032). The results indicate that the LT
alpha gene, or a closely linked locus, is associated with atopy, and sugge
st a sex difference in the effect of the gene.