TUMOR-NECROSIS-FACTOR HAPLOTYPES AND ASTHMA

Airway inflammation is a prominent feature of asthma. The pro-inflamma tory cytokine Tumour Necrosis Factor shows constitutional variation in its level of secretion, which is linked to polymorphisms within the T NF gene complex and the surrounding MHC, In this study, 413 subjects i n 88 nuclear families from a general population sample were examined f or association with asthma and TNF polymorphisms, Ninety-two subjects were asthmatic, as defined by questionnaire, Asthma was significantly more common in subjects with allele 1 of the LT alpha Ncol polymorphis m (LT alpha Ncol1) (p = 0.005), and allele 2 of the TNF-308 polymorph ism (TNF-3082) (p = 0.004), The association was confined to the LT al pha Ncol1/TNF308*2 haplotype, so that it was not possible to differen tiate between the effects of LT alpha Ncol and TNF-308 alleles. The HL A-DR locus was excluded as a cause of this association, The results su ggest that genetic influences on inflammation may be important in the pathogenesis of asthma.