The influence of genetic variability in IL1B and MIR146A on the risk of pleural plaques and malignant mesothelioma

Abstract

BackgroundAsbestos exposure is associated with the development of pleural plaques as well as malignant mesothelioma (MM). Asbestos fibres activate macrophages, leading to the release of inflammatory mediators including interleukin 1 beta (IL-1β). The expression of IL-1β may be influenced by genetic variability of IL1B gene or regulatory microRNAs (miRNAs). This study investigated the effect of polymorphisms in IL1B and MIR146A genes on the risk of developing pleural plaques and MM.Subjects and methodsIn total, 394 patients with pleural plaques, 277 patients with MM, and 175 healthy control subjects were genotyped for IL1B and MIR146A polymorphisms. Logistic regression was used in statistical analysis.ResultsWe found no association between MIR146A and IL1B genotypes, and the risk of pleural plaques. MIR146A rs2910164 was significantly associated with a decreased risk of MM (OR = 0.31, 95% CI = 0.13–0.73, p = 0.008). Carriers of two polymorphic alleles had a lower risk of developing MM, even after adjustment for gender and age (OR = 0.34, 95% CI = 0.14–0.85, p = 0.020). Among patients with known asbestos exposure, carriers of at least one polymorphic IL1B rs1143623 allele also had a lower risk of MM in multivariable analysis (OR = 0.50, 95% CI = 0.28–0.92, p = 0.025). The interaction between IL1B rs1143623 and IL1B rs1071676 was significantly associated with an increased risk of MM (p = 0.050).ConclusionsOur findings suggest that genetic variability of inflammatory mediator IL-1β could contribute to the risk of developing MM, but not pleural plaques.

CARD8 and IL1B Polymorphisms Influence MRI Brain Patterns in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Hypothermia

“…On the other hand, IL1B rs1143623 was associated with Alzheimer’s disease pathology [ 63 ] and response to biological treatment in psoriasis [ 64 ]. The role of IL1B rs1071676 is not well established, but it could affect miRNA binding [ 65 ], and it was associated with response to anti-TNF therapy [ 66 ]. Previous findings are therefore consistent with our results as we have also shown an association between IL1B rs1143623 and IL1B rs16944 and more basal ganglia and PLIC abnormalities based on MRI pattern.…”

The Evolving Landscape of the Molecular Epidemiology of Malignant Pleural Mesothelioma

“…Up until now, few data are available on miRNA polymorphisms in MPM. In a cohort of asbestos-exposed subjects, detection of miRN-146A rs2910164 polymorphism has been significantly associated with risk of MPM onset since carriers of two polymorphic alleles features lower risk of disease development [ 127 ]. Within an extensive occupational surveillance program on workers previously exposed to asbestos, researchers documented, with potential diagnostic and prognostic implications, that the rs1057147 variant within the 3′UTR of the mesothelin ( MSLN ) gene could be a putative miRSNP and that MSLN is a candidate target of miR-611 and, to a lesser extent, of miR-887 [ 128 ].…”