Polymorphisms in the tumour necrosis factor alpha-induced protein 3 (TNFAIP3) gene are associated with chronic rhinosinusitis.

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.