Association of HLA and cytokine gene polymorphisms with idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a rare, progressive, and lethal interstitial lung disease with unknown etiology. Divergent observations have suggested that genetic factors contribute to IPF susceptibility. This study investigated the relationship between human leukocyte antigen (HLA), cytokine gene polymorphisms, and IPF in a Chinese Han population. The gene polymorphisms of HLA-A, -B, -DRB1, tumor necrosis factor alpha [TNF-α (-308 A/G)], transforming growth factor beta [TGF-β1 (+869 T/C)], interleukin 10 [IL-10 (-592 C/A, -819 T/C, and -1082 G/A)], and interferon gamma [IFN-γ (+874 T/A)] were detected in 102 individuals with IPF and 266 unrelated normal controls using PCR with sequence-specific primers and a high-resolution melt (HRM) approach. The data showed that there was no difference in HLA allele frequencies between the IPF and control groups. However, the data showed the frequency of HLA-A*02-DRB1*04 haplotype in the IPF group was significantly higher than that in the control group [odds ratio (OR) = 4.69, 95% confidence interval (CI) = 1.82-12.08, p < 0.001]. In addition, no differences in the allele and genotype distributions of the cytokines were found between the IPF and control groups (p > 0.01). Our findings suggest that there is an association between specific HLA haplotype and IPF genetic susceptibility and that the genetic variability of some cytokines may not be involved in the pathogenesis of IPF.

The association between transforming growth factor beta1 polymorphism and susceptibility to pulmonary fibrosis

“…However, several other studies could not find any noticeable association of TGF-β1 rs1800470 polymorphism with pulmonary fibrosis. [ 19 , 21 , 22 , 27 ]…”

Genetics in Idiopathic Pulmonary Fibrosis Pathogenesis, Prognosis, and Treatment

“…Several studies have also implicated the human leukocyte antigen (HLA) region in IPF ( 85 – 89 ). The HLA region is located on chromosome 6p21.31 ( 90 ), and its main function is regulation of immune response.…”

“…The HLA region is located on chromosome 6p21.31 ( 90 ), and its main function is regulation of immune response. The DRB1*15:01 allele has been shown to be more prevalent among IPF patients and associated with greater impairment of gas exchange ( 89 ). Recently, a genome-wide imputation-based association analysis identified two risk alleles, DRB1*15:01 and DQB1*06:02, found to be associated with fibrotic idiopathic interstitial pneumonias ( 48 ).…”

FOXP3polymorphisms in interstitial lung disease among Chinese Han population: A genetic association study

“…However, the etiopathogenesis of most ILD entities remain unknown. A recent genome-wide association study (GWAS) identified a number of polymorphisms associated with ILD 9 ; gene mutations in surfactant proteins (including SP-A, -B, -C and -D), 10 mucin 5B gene (MUC5B), 11 major histocompatibility complex (MHC) 12 and telomerase reverse transcriptase 13 are also associated with increased risk of ILD. 8 Autoimmune diseases, lung inflammation, radiation therapy to the chest and occupational exposure to asbestos-containing materials may also trigger disease onset in susceptible individuals.…”

“…Genetic factors have also been shown to contribute to ILD pathogenesis on exposure to a variety of triggers, and the role of genetic polymorphisms in ILD has drawn increasing attention in recent years. A recent genome-wide association study (GWAS) identified a number of polymorphisms associated with ILD 9 ; gene mutations in surfactant proteins (including SP-A, -B, -C and -D), 10 mucin 5B gene (MUC5B), 11 major histocompatibility complex (MHC) 12 and telomerase reverse transcriptase 13 are also associated with increased risk of ILD. However, this association of genetic polymorphisms with ILD remains controversial in different populations.…”