Unraveling the genetic component of systemic sclerosis

Abstract

Systemic sclerosis (SSc) is a severe connective tissue disorder characterized by extensive fibrosis, vascular damage, and autoimmune events. During the last years, the number of genetic markers convincingly associated with SSc has exponentially increased. In this report, we aim to offer an updated review of the classical and novel genetic associations with SSc, analyzing the firmest and replicated signals within HLA and non-HLA genes, identified by both candidate gene and genome-wide association (GWA) studies. We will also provide an insight into the future perspectives and approaches that might shed more light into the complex genetic background underlying SSc. In spite of the remarkable advance in the field of SSc genetics during the last decade, the use of the new genetic technologies such as next generation sequencing (NGS), as well as the deep phenotyping of the study cohorts, to fully characterize the genetic component of this disease is imperative.

Genetic risk factors for sclerotic graft-versus-host disease

“…4,6 To date, genetic risk factors for sclerotic GVHD have not been well defined, but candidate gene and genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) associated with systemic sclerosis. 7 These SNPs include HLA and non-HLA variants involved in adaptive and innate immune responses. We hypothesized that the same SNPs might also have associations with the development of sclerosis in patients with chronic GVHD if the two diseases have similar pathogenic mechanisms.…”

Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis

“…In sarcoidosis the development of irreversible lung fibrosis, seen in 10–20% of patients, is associated with poorer quality of life, the need for long-term treatment and a worse prognosis 8. A small number of genes associated with the development of lung fibrosis in the context of SSc9 or of sarcoidosis10–12 have been reported, highlighting a genetic component likely to involve several genes with small individual effects. Although SSc-associated interstitial lung disease (SSc-ILD) and pulmonary sarcoidosis differ from IPF in many respects, including better survival for equivalent disease severity,13 there are many similarities in the fibrotic process and alveolar epithelium abnormalities occur in all three diseases.…”

New insight on the Xq28 association with systemic sclerosis

“…In some cases, part of the genetic component is shared among different immune disorders, suggesting that these pathologies may be influenced by disease-specific and common molecular pathways 1–4. For instance, most of the genetic associations described for systemic sclerosis (SSc), a fibrotic autoimmune disease of skin and internal organs, have also been reported to play a role in the susceptibility to systemic lupus erythematosus (SLE) 5 6…”