SSc-related Interstitial Lung Disease Not Linked to Idiopathic Interstitial Pneumonia

Analyzing data from a genome-wide association study (GWAS), a team led by researchers at the University of Texas McGovern Medical School at Houston showed that systemic sclerosis (SSc)-related interstitial lung disease (ILD) is not genetically linked to idiopathic interstitial pneumonia.

SSc-ILD has clinical and radiological similarities to idiopathic interstitial pneumonia, and researchers have suspected that the conditions might share genetic underpinnings. Genetic factors are known to contribute both to SSc susceptibility and the risk of specific SSc clinical types. But while SSc-ILD and idiopathic interstitial pneumonia share symptoms, recent studies have suggested that the genetic risk factors for these two conditions are quite different.

Earlier research showed that a mutation in the MUC5B gene was strongly associated with familial and idiopathic pulmonary fibrosis, the most common kind of idiopathic interstitial pneumonia. No studies have, however, linked the gene to SSc or SSc-ILD.

Recently, GWAS data from idiopathic interstitial pneumonia and idiopathic pulmonary fibrosis patients identified 15 mutations in different genes that associated with disease. The data were also confirmed in subsequent replication studies.

In the current study, the research team led by Minghua Wu analyzed associations between 13 of these mutations and SSc-ILD, as well as disease severity, in data from another GWAS of SSc patients. The study, “Genetic susceptibility loci of idiopathic interstitial pneumonia do not represent risk for systemic sclerosis: a case control study in Caucasian patients,” was published in the journal Arthritis Research and Therapy.

An initial analysis of 1,486 SSc patients and 3,477 healthy controls from the U.S. discovery GWAS revealed associations between two gene variants and SSc, and one gene variant and SSc-ILD, determined by imaging. Another three gene variants were associated with percent predicted forced vital capacity.

When the researchers repeated the analysis in a replication cohort, consisting of 1,085 SSc patients and 1,023 healthy controls, the team could no longer detect the associations, neither to disease nor to forced vital capacity.

The study confirmed that SSc-ILD and idiopathic interstitial pneumonia are different diseases, not sharing a genetic basis. Earlier studies showed that immune pathways are implicated in SSc, whereas interstitial pneumonia is related to epithelial cell injury or dysfunction and abnormal wound healing.

This study is an important step toward a better understanding of the genetics behind SSc with lung involvement.