Genetic Factors in Systemic Sclerosis

Overview

Journal Arthritis Res Ther

Publisher Biomed Central

Specialty Rheumatology

Date 2007 Sep 15

PMID 17767743

Citations 11

Authors

Maureen D Mayes

Maria Trojanowska

Affiliations

Soon will be listed here.

Abstract

A number of genetic loci have been identified that appear to be associated with systemic sclerosis (SSc; scleroderma). There is mounting evidence suggesting that these genetic associations may in fact be associated with distinct phenotypes in SSc based on autoantibody pattern rather than with SSc as a single disease entity. This may ultimately have implications for approaches to therapy as well as responses to therapy. The most promising candidate genes are those involved in pathways that lead to the vascular damage and fibrosis that are the hallmarks of this disease. There is uncertainty, however, regarding the nature of the key pathological mechanisms that link these two disease processes. Recent studies have focused on Fli1 (friend leukaemia integration 1), a transcription factor that is found in immune cells, fibroblasts, and endothelial cells that regulates collagen gene function and angiogenesis. Fli1 is dysregulated in SSc skin and dermal blood vessels, and appears to play a pathological role in SSc skin fibrosis and vessel degeneration. Whether this dysregulation is due to genetic polymorphisms in the Fli1 pathway or to epigenetic mechanisms is not clear.

Citing Articles

Fli1 and Tissue Fibrosis in Various Diseases.

Mikhailova E, Romanova I, Bagrov A, Agalakova N Int J Mol Sci. 2023; 24(3).

PMID: 36768203 PMC: 9915382. DOI: 10.3390/ijms24031881.

Impact of Human Cytomegalovirus and Human Herpesvirus 6 Infection on the Expression of Factors Associated with Cell Fibrosis and Apoptosis: Clues for Implication in Systemic Sclerosis Development.

Arcangeletti M, DAccolti M, Maccari C, Soffritti I, De Conto F, Chezzi C Int J Mol Sci. 2020; 21(17).

PMID: 32899126 PMC: 7504027. DOI: 10.3390/ijms21176397.

Analysis of killer cell immunoglobulin-like receptors (KIRs) and their HLA ligand genes polymorphisms in Iranian patients with systemic sclerosis.

Mahmoudi M, Fallahian F, Sobhani S, Ghoroghi S, Jamshidi A, Poursani S Clin Rheumatol. 2017; 36(4):853-862.

PMID: 28120169 DOI: 10.1007/s10067-016-3526-0.

Endothelin receptor blockade ameliorates vascular fragility in endothelial cell-specific Fli-1-knockout mice by increasing Fli-1 DNA binding ability.

Akamata K, Asano Y, Yamashita T, Noda S, Taniguchi T, Takahashi T Arthritis Rheumatol. 2015; 67(5):1335-44.

PMID: 25707716 PMC: 4784268. DOI: 10.1002/art.39062.

Angiotensin receptor type 1 and endothelin receptor type A on immune cells mediate migration and the expression of IL-8 and CCL18 when stimulated by autoantibodies from systemic sclerosis patients.

Gunther J, Kill A, Becker M, Heidecke H, Rademacher J, Siegert E Arthritis Res Ther. 2014; 16(2):R65.

PMID: 24612997 PMC: 4060229. DOI: 10.1186/ar4503.

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