title: IL1 gene cluster polymorphisms and its haplotypes may predict the risk to develop invasive pulmonary aspergillosis and modulate C-reactive protein level.
abstract: OBJECTIVE
  The aim of this study was to determine whether interleukin-1 alpha (IL1alpha), interleukin-1 beta (IL1beta), and IL1 receptor antagonist (IL1Ra) polymorphisms are implicated in invasive pulmonary aspergillosis (IPA) pathogenesis.
  
  
  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).
  
  
  CONCLUSIONS
  Individual locus analysis showed that IL1alpha 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 IL1beta( - ) (511TT) genotype (or IL1beta(-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 IL1beta(-511)T/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.
  
  
  CONCLUSIONS
  These findings indicate a critical role of IL1 gene cluster polymorphisms in the susceptibility to IPA infection and CRP production.
authors.affiliation: Unidad de Investigación, Hospital Universitario Virgen de las Nieves, Granada, Spain. jsainz@ugr.es
authors.forename: J
authors.initials: J
authors.lastname: Sainz
authors.forename: E
authors.initials: E
authors.lastname: Pérez
authors.forename: S
authors.initials: S
authors.lastname: Gómez-Lopera
authors.forename: M
authors.initials: M
authors.lastname: Jurado
mesh_terms: D001228:Aspergillosis / Q000097:blood / Q000209:etiology / Q000235:genetics*; D001230:Aspergillus / Q000276:immunology; D002097:C-Reactive Protein / Q000378:metabolism; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D019337:Hematologic Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy; D006801:Humans; D016867:Immunocompromised Host; D053582:Interleukin-1alpha / Q000097:blood / Q000235:genetics* / Q000276:immunology; D053583:Interleukin-1beta / Q000097:blood / Q000235:genetics* / Q000276:immunology; D008172:Lung Diseases, Fungal / Q000097:blood / Q000209:etiology / Q000235:genetics*; D008297:Male; D008351:Mannans / Q000097:blood; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D053573:Receptors, Interleukin-1 Type I / Q000097:blood / Q000235:genetics* / Q000276:immunology; D013223:Statistics as Topic
chemical_list: D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D008351:Mannans; D053573:Receptors, Interleukin-1 Type I; C012990:galactomannan; D002097:C-Reactive Protein; D005690:Galactose