Background: Factors conferring susceptibility to chronic rhinosinusitis remain unknown. However, advances in genomics offer powerful tools to explore this disorder. Tumour necrosis factor (TNF) is a crucial proinflammatory cytokine that exerts inflammatory and immunomodulatory activities important in host defense. Our objective was to determine whether polymorphisms in genes in the TNF superfamily (TNF, TNF-alpha-induced protein 3, TNF-alpha-induced protein 6) were associated with chronic rhinosinusitis.
Methods: Deoxyribonucleic acid (DNA) extracted from a population of 206 patients with severe chronic rhinosinusitis and 196 postal code-matched controls was used. Three candidate genes related to the TNF inflammatory pathway were assessed. For each gene, an informative set of single nucleotide polymorphisms was genotyped.
Results: Thirty-five single nucleotide polymorphisms were genotyped. Two polymorphisms located within the TNF-alpha-induced protein 3 gene (TNFAIP3) reached the nominal p value threshold (p < .05) for association with chronic rhinosinusitis. However, none of these polymorphisms resist multiple testing adjustments.
Conclusions: Our data suggest that two polymorphisms in TNFAIP3 are weakly associated with severe chronic rhinosinusitis but do not support an association with genetic variants in TNF or TNF-alpha-induced protein 6. Although these results do not support correction for multiple testing and have to be validated in a second population, they nevertheless suggest that further studies of the role of TNFAIP3 in the pathogenesis of disease are warranted.