Background Bullous pemphigoid (BP) is an autoimmune bullous disease mostly associated with autoantibodies to the hemidesmosomal BP autoantigens BP180 and BP230. High levels of interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, tumour necrosis factor (TNF)-α and interferon (IFN)-γ have been detected in skin lesions or sera of patients with BP. Cytokine gene polymorphisms may affect cytokine production and contribute to susceptibility to autoimmune diseases. Until now, no cytokine gene polymorphism study has been conducted on patients with BP.
Objectives We aimed to determine whether the genetic polymorphisms of the cytokine genes might influence the development of BP.
Methods DNA samples were obtained from 96 BP patients and 174 control subjects. Using direct sequencing and microsatellite genotyping, we examined 23 polymorphisms in 11 cytokine genes including the IL-1α, IL-1β, IL-1 receptor antagonist, IL-4, IL-6, IL-8, IL-10, IL-13, IL-4 receptor, TNF-α and IFN-γ genes.
Results Although the BP patients were more likely to carry the −511T and −31C alleles of the IL-1β gene (P = 0·04), the significance disappeared after correction for multiple testing (Pc). There was complete linkage disequilibrium between the −511T and −31C alleles of the IL-1β gene. In female patients with BP, the associations with IL-1β (−511T) and (−31C) alleles were much stronger (68% vs. 40·6%, odds ratio = 3·11, Pc = 0·006). No significantly different allelic and genotypic distributions of other cytokine gene polymorphisms could be found between the patients with BP and controls. Moreover, no association with the extent of disease involvement (localized or generalized) was observed.
Conclusions The IL-1β (−511) and (−31) polymorphisms were significantly associated with BP in women. The other genetic polymorphisms of cytokine genes that we analysed do not appear to be associated with BP susceptibility in our Chinese population.