Tumour necrosis factor (TNF) is a proinflammatory cytokine that increases human airway tissue responsiveness and is considered a candidate gene for asthma. Two common polymorphisms (LTalphaNcoI and TNFalpha-308) in the TNF gene complex were studied in 600 subjects from 131 Italian families with atopic asthmatic children. Skin prick test (SPT), total IgE levels, atopy (defined as increased IgE levels or SPT positivity or both), bronchial hyperresponsiveness, and clinical asthma were investigated. The observed distribution of the identical by descent alleles at the LTalphaNcoI locus was different from expected for SPT and atopy (p=0.015). The LTalphaNcoI genotype distribution for increased IgE levels was different between males and females (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 LTalpha gene, or a closely linked locus, is associated with atopy, and suggest a sex difference in the effect of the gene.
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