Association between-308 tumour necrosis factor promoter polymorphism and bronchial hyperreactivity in asthma

Background Tumour necrosis factor (TNF) is a pivotal cytokine in the inflam mation underlying asthma. The TNF gene is located in the polymorphic HLA cl ass 3 region on chromosome 6p. Several polymorphisms in this region have be en described and associated with alteration of TNF secretion in vitro. Objective In this study we tested the hypothesis that two such polymorphism s, lymphotoxin alpha NcoI B*1 and - 308 TNF2 may be components of the genet ic predisposition to asthma. Methods Five hundred and fifty-six random individuals were studied, compris ing approximately equal numbers of asthmatic subjects, with or without atop y, and a nonatopic nonasthmatic control group. In addition, 355 subjects (1 72 asthmatics) from 60 multiplex families were typed at the LT alpha NcoI l ocus. Results There was an association between allele two of the - 308 TNF polymo rphism and bronchial hyperreactivity (OR 2.12, 95% CI 1.04-4.32, P = 0.036) . However, there was no association with LT alpha NcoI alleles. To determin e whether this was influenced by linkage disequilibrium within the MHC, 91 subjects with bronchial hyperreactivity and 85 control subjects were typed for class 2 and 3 alleles. Following identification of the extended TNF2 ha plotype, we found no independent association of these alleles with BHR. Conclusions We conclude that the - 308 TNF2 promoter polymorphism may form a component of the genetic predisposition to BHR in asthma.