Lack of association between cytokine gene polymorphisms and silicosis and pulmonary tuberculosis in Chinese iron miners

Abstract

Silicosis is a fibrotic lung disease produced by the inhalation and deposition of silica dust. The association between silicosis and pulmonary tuberculosis (PTB) has been well established. Cytokines participate in the development and progression of silicosis and PTB. Functional polymorphisms in cytokine genes have been identified that alter cytokine production. The aims of the current investigation were to determine whether functional polymorphisms in the tumor necrosis factor-alpha (TNF-alpha) gene at position -308; in the transforming growth factor-beta 1 (TGF-beta1) gene at positions -509, +869 (codon 10), and +915 (codon 25); in the interleukin-10 (IL-10) gene at position -1,082, -819 and -592; and in the intron 1 of the interferon-gamma (IFN-gamma) gene at position +874 are associated with silicosis and PTB. We conducted a case-control study with 183 silicosis patients and 111 silica-exposed miners, and a 1:2 matched case-control study of 61 PTB cases and 122 PTB-free miners. Genotype analysis was performed on genomic DNA, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. There was complete linkage disequilibrium (LD) between the -819C and -592C alleles of the IL-10 gene. The genotype frequencies were similar between cases and control subjects for all investigated cytokine polymorphisms (p>0.05). We did not find an association between the different genotypes and severity of silicosis. We assume that these genetic variants do not play a dominant role in silicosis and PTB in our Chinese population.