IL1 Gene Cluster Polymorphisms and Its Haplotypes may Predict the Risk to Develop Invasive Pulmonary Aspergillosis and Modulate C-reactive Protein Level
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The aim of this study was to determine whether interleukin-1 alpha (IL1α), interleukin-1 beta (IL1β), 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 IL1α 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 IL1β - 511TT genotype (or IL1β-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 IL1β-511T/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.
These findings indicate a critical role of IL1 gene cluster polymorphisms in the susceptibility to IPA infection and CRP production.
KeywordsIL1 cluster polymorphisms susceptibility IPA CRP galactomannan
We are indebted to the patients and healthy controls who participated in this study. The advice of Dr. Victor Moreno (Catalan Institute of Oncology) on the development of the genetic tests is acknowledged. The authors thank C. González Moreno (leukemia survivor) for her generous donation, Elena Lamas (laboratory technician) for sample collection and technical support, and staff of the Research Unit of Virgen de las Nieves University Hospital for providing the necessary facilities. This study was supported by a grant (259/04) from the Servicio Andaluz de Salud (SAS), a grant from Fundación anti-cancer San Francisco Javier y Santa Cándida, and a postdoctoral training grant from the Fundación para la Investigación Biosanitaria de Andalucía Oriental-Alejandro Otero (FIBAO).
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