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

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 (LTáNcoI and TNFá-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 LTáNcoI locus was diVerent from expected for SPT and atopy (p=0.015). The LTáNcoI genotype distribution for increased IgE levels was diVerent 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 LTá gene, or a closely linked locus, is associated with atopy, and suggest a sex diVerence in the eVect of the gene. (J Med Genet 1999;36:323–325)