Human Fibrosis: Is There Evidence for a Genetic Predisposition in Musculoskeletal Tissues?

Background: Pathologic fibrosis is characterized by dysregulation of gene expression with excessive extracellular matrix production. The genetic basis for solid organ fibrosis is well described in the literature. However, there is a paucity of evidence for similar processes in the musculoskeletal (MSK) system. The purpose of this review is to provide an overview of existing evidence of genetic predisposition to pathologic fibrosis in the cardiac, pulmonary, and MSK systems, and to describe common genetic variants associated with these processes.

Methods: A comprehensive search of several databases from 2000 to 2019 was conducted using relevant keywords in the English language. Genes reported as involved in idiopathic fibrotic processes in the heart, lung, hand, shoulder, and knee were recorded by 2 independent authors.

Results: Among 2373 eligible studies, 52 studies investigated genetic predisposition in terms of variant analysis with the following organ system distribution: 36 pulmonary studies (69%), 15 hand studies (29%), and 1 knee study (2%). Twenty-two percent of gene variants identified were associated with both pulmonary and MSK fibrosis (ie, ADAM, HLA, CARD, EIF, TGF, WNT, and ZNF genes). Genetic variants known to be involved in the MSK tissue development or contractility properties in muscle were identified in the pulmonary fibrosis.

Conclusion: Despite shared genetic variations in both the lung and hand, there remains limited information about genetic variants associated with fibrosis in other MSK regions. This finding establishes the necessity of further studies to elucidate the genetic determinants involved in the knee, shoulder, and other joint fibrotic pathways.

Level of evidence: Level III.