IL1 gene cluster polymorphisms and its haplotypes may predict the risk to develop invasive pulmonary aspergillosis and modulate C-reactive protein level

Objective The aim of this study was to determine whether interleukin-1 alpha (IL1 alpha), interleukin-1 beta (IL1 beta), and IL1 receptor antagonist (IL1Ra) polymorphisms are implicated in invasive pulmonary aspergillosis (IPA) pathogenesis. Materials and Methods Subjects comprised 110 hematological patients and 148 healthy controls. Genotypic and allelic frequencies were similar between hematological patients and controls. IPA was diagnosed in 59 of the 110 patients according to consensus criteria published by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group (EORTC/IFICG). Results and Discussions Individual locus analysis showed that IL1 alpha and IL1Ra polymorphisms were not associated with the presence of IPA (p=0.560 and p=0.680, respectively). However, a trend towards a higher presence of IL1 beta(-511TT) genotype (or IL1 beta(-511T) allele) in the IPA group than in the non-IPA patient group (p=0.092 and p=0.095, respectively) was found. Haplotype analysis revealed that VNTR2/-889C/-511T haplotype was strongly associated with susceptibility to develop IPA infection (p=0.020). Haplotype analysis also showed an association between VNTR2/-889C/-511C haplotype and resistance to IPA infection (p=0.028). Furthermore, patients with IL1Ra VNTR2/2 and IL1 beta T-511/T genotypes had a higher positive serum galactomannan percentage versus patients with other genotypes. Finally, C-reactive protein (CRP) production was significantly associated with IL1 gene cluster polymorphisms, although CRP values were similar between IPA and non-IPA groups. Conclusion These findings indicate a critical role of IL1 gene cluster polymorphisms in the susceptibility to IPA infection and CRP production.