Genetic variants of IL6 gene promoter influence on C-reactive protein levels but are not associated with susceptibility to invasive pulmonary aspergillosis in haematological patients

Abstract

Several lines of evidence indicate that IL6 plays a major role in the pathogenesis of a number of infectious diseases. The purpose of this study was to determine whether IL6 promoter polymorphisms were genetic markers of susceptibility to invasive pulmonary aspergillosis (IPA). To clarify the relationship between IL6 variants and IPA susceptibility, the IL6-174(G/C) and IL6-634(G/C) promoter single nucleotide polymorphisms (SNPs) were defined and plasma concentrations of IL6 and C-reactive protein (CRP) were measured. The study included 130 patients with haematological malignancies and 145 unrelated healthy individuals. No significant genotypic and allelic differences were found between patients and healthy controls. IPA was diagnosed in 71 of 130 patients according to the consensus criteria. CRP values were significantly associated with both IL6-174(G/C) and IL6-634(G/C) polymorphisms. However, IL6 and CRP values were similar between IPA and non-IPA groups. Neither IL6-174(G/C) nor IL6-634(G/C) polymorphisms were associated with IPA infection (p=0.414 and p=0.184, respectively). No evidence of association was found between allelic frequencies of IL6 promoter polymorphisms and IPA infection (p=0.864 and p=0.104, respectively). Further, no association was detected between IL6 genotypes and clinical profiles in IPA patients. Haplotype analysis also revealed that IL6 gene was not associated with IPA susceptibility in a Spanish population (Global haplotype association p value: 0.31). These findings suggest that IL6 polymorphisms influence on CRP circulating levels but are not associated with IPA susceptibility. Because the sample size is relatively small in our series, larger investigations of IL6-174(G/C)/IL6-634(G/C) genotypes and haplotypes are needed to clarify the potential role of this gene in the pathophysiology of IPA infection.