Genetic susceptibility to systemic sclerosis from clinical aspect to genetic factor analyses

Eur J Intern Med. 2009 May;20(3):242-52. doi: 10.1016/j.ejim.2008.07.012. Epub 2008 Sep 11.


Background: Systemic sclerosis is a rare autoimmune disease mainly characterized by vascular alteration and fibrosis involving skin but also visceral organs such as lungs, digestive tract, and heart. This disease leads to high morbidity and mortality. Its pathogenesis remains unclear, but recent attention has focus on genetic factors.

Objective: We first recall the main manifestations associated with systemic sclerosis and leading to its diagnosis and prognosis. Then we propose an overview on human genetics studies, as a number of genetic loci have been identified that appear to be associated with the disease.

Methods: Articles concerning association studies with candidate genes encoding for extracellular matrix proteins, cytokines, growth factors, chemokines, and proteins involved in vascular tone and immune regulations are presented and discussed.

Results/conclusion: Systemic sclerosis is a multigenic complex disorder. Genetic associations are observed in distinct phenotypes such as the diffuse cutaneous form or the limited form, or in association with specific autoantibody pattern. Promising candidate genes are those involved in pathways that lead to the vascular damage and fibrosis. A better knowledge of crucial mediators involved in systemic sclerosis could in the future provide new therapeutic strategies to control the disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Genetic Predisposition to Disease*
  • Humans
  • Polymorphism, Genetic
  • Risk Factors
  • Scleroderma, Systemic / epidemiology
  • Scleroderma, Systemic / genetics*
  • Scleroderma, Systemic / immunology*