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Review
. 2013 Dec 18:4:159.
doi: 10.3389/fphar.2013.00159.

Genetic architecture of human fibrotic diseases: disease risk and disease progression

Agnès Gardet  1 , Timothy S Zheng  1 , Joanne L Viney  1
Affiliations
Review

Genetic architecture of human fibrotic diseases: disease risk and disease progression

Agnès Gardet et al. Front Pharmacol. .

Abstract

Genetic studies of human diseases have identified multiple genetic risk loci for various fibrotic diseases. This has provided insights into the myriad of biological pathways potentially involved in disease pathogenesis. These discoveries suggest that alterations in immune responses, barrier function, metabolism and telomerase activity may be implicated in the genetic risks for fibrotic diseases. In addition to genetic disease-risks, the identification of genetic disease-modifiers associated with disease complications, severity or prognosis provides crucial insights into the biological processes implicated in disease progression. Understanding the biological processes driving disease progression may be critical to delineate more effective strategies for therapeutic interventions. This review provides an overview of current knowledge and gaps regarding genetic disease-risks and genetic disease-modifiers in human fibrotic diseases.

Keywords: GWAS; auto-immunity; disease progression; fibrosis; genetics.

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Figures

Figure 1
Figure 1
Effect of pulmonary fibrosis on lung architecture. The architecture of the lung in idiopathic pulmonary fibrosis (IPF) is characterized by a so-called “honeycomb” pattern with airways separated by bands of inflamed fibrous connective tissue and to a lesser extent, smooth muscle. The modifications of the lung architecture induced by the fibrosis lead to compromised diffusion of oxygen and carbon dioxide and impaired pulmonary function. Hematoxylin and eosin staining of human normal lung and IPF lung (scale bar = 100 um). Courtesy of Dr. Robert Dunstan.
Figure 2
Figure 2
Selected genes located in genetic risk loci associated with higher susceptibility for diseases with fibrotic complications. Genetic studies have successfully identified numerous genetic risk loci associated with higher susceptibility for diseases associated with fibrosis. Left panel displays diseases associated with a strong immune component and the genetic risk loci implicated in at least three of these diseases. Right panel displays diseases associated with risk loci implicating genes involved in non-immune function, such as barrier and metabolic functions.
Figure 3
Figure 3
Overview of biological processes and pathways proposed to be associated with disease risk and disease progression. Left panel shows the biological processes associated with the genes located in the risk loci associated with higher susceptibility for disease. Right panel shows the biological pathways associated with genes located in the loci associated with disease progression. Further genetic studies of disease progression are needed to confirm initial results from limited sample sizes. SSc, systemic#sclerosis; PSC, primary sclerosing cholangitis; PBC, primary biliary cirrhosis; T1D, type 1 diabetes; T2D, type 2 diabetes; IBD, inflammatory bowel disease; IIP, idiopathic interstitial pneumonias; CKD, chronic kidney disease; NAFLD, non-alcoholic fatty liver disease; ILD, interstitial lung disease; IPF, idiopathic pulmonary fibrosis.
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