Association of a lymphotoxin alpha gene polymorphism and atopy in Italian families

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.