PURPOSE: We sought to identify an association between gene polymorphisms in the interleukin-6 (IL-6), IL-10, transforming growth factor (TGF)-β 1, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ genes, and high-resolution computed tomography (HRCT) patterns in patients with interstitial lung disease.
METHODS: We included patients diagnosed with idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), and pulmonary fibrosis associated with collagen disease (PF/CD). Cytokine genotypes were determined using polymerase chain reaction (PCR) sequence-specific primers. HRCT images were obtained on the day on which blood samples were taken. These images were assessed for presence or absence of honeycombing (HC), architectural distortion (AD), reticulation, traction bronchiectasis, and ground-glass opacity.
RESULTS: Seventy-five patients with interstitial lung disease (IPF, n=44; NSIP, n=13; PF/CD, n=18) were studied. Individuals with G/G homozygosity at the TNF-α (-308) position were at higher risk of HC compared to those without HC (67.7% vs. 38.5%, odds ratio [OR] 3.4; 95% confidence interval [CI] 0.97-11.6; p=0.047). G/A individuals heterozygous at TNF-α (-308) were at lower risk of HC (HC absent 61.5% vs. HC present 25.8%, OR 0.22; 95% CI 0.06-0.76; p=0.012). Moreover, patients with the GCC/GCC genotype at IL-10 (-1082), (-819), and (-592) positions were at lower risk of HC (HC absent 46.2% vs. HC present 17.7%, OR 0.25; 95% CI 0.07-0.89; p=0.026). Comparison of patients with and without AD revealed that the former were at significantly higher risk in individuals showing G/G homozygosity in the TNF-α gene (AD present 67.7% vs. AD absent 22.2%; OR 7.3; 95% CI 1.4-38.4; p=0.008). G/A individuals heterozygous at this position were at lower risk of AD (AD absent 77.8% vs. AD present 26.2%; OR 0.1; 95% CI 0.02-0.53; p=0.002). Other CT parameters were not associated with any marked difference in cytokine gene polymorphism.
CONCLUSION: Significant association of polymorphisms in the TNF-α , and IL-10 genes with HRCT patterns shown by patients with advanced interstitial lung disease.
CLINICAL IMPLICATIONS: Association of cytokine gene polymorphisms with HRCT pattern may contribute to the pathogenesis of fibrotic lung disease.
DISCLOSURE: Esam Alhamad, No Financial Disclosure Information; No Product/Research Disclosure Information