The IL - 6 promoter polymorphism is associated with disease activity and disability in systemic sclerosis

Abstract

Systemic sclerosis (SSc) is a rare, autoimmune disease characterized by cutaneous and visceral fibrosis. Interleukin-6 (IL-6) is involved in the pathogenesis of many immune-mediated diseases. IL-6 plays an important role in the initiation and promotion of fibrosis. The polymorphism in the position -174 (G/C) of the promoter region of the IL-6 gene (IL-6 pr) may alter the expression of the gene. Complete linkage disequilibrium was observed between the -174 and -597 alleles. The aim of this study is to investigate the possible influence of -597 (-174) IL-6 pr polymorphism on the susceptibility and/or the clinical course of SSc in Romanian population. Genotyping of -597 variant was performed by an RFLP method on 20 SSc patients and 26 healthy subjects. Patients having the homozygous GG (-597) genotype had higher disease activity and disability scores than heterozygous GA patients: the European Scleroderma Study Group (EScSG) disease activity score was 5.0 ± 3.3 in homozygous GG subjects vs. 2.4 ± 3.6 in heterozygous GA patients (p < 0.05), and the Disability Index of the Health Assessment Questionnaire (HAQ-DI) was 1.42 ± 1.04 in homozygous GG subjects vs. 0.53 ± 0.55 in heterozygous GA patients (p < 0.05). No difference was observed in the distribution of allele frequencies between SSc patients and healthy controls. Conclusions: The GG homozygosis was found to be associated with a higher degree of illness activity and disability in SSc patients. No statistically significant differences were found between SSc patients and healthy controls with respect to the -597 allele distribution.

The Role of Type 1 Interferon in Systemic Sclerosis

“…It is involved in the pathogenesis of many immune-mediated diseases including SSc (89–91). IL-6 is a classic inflammatory cytokine produced by various cells and involved in B cell differentiation, induction of acute phase proteins in liver cells, proliferation, and differentiation of T cells (92, 93).…”

Association between rs1800795 (-174 G/C) Polymorphism in the Promoter of &lt;i&gt;IL&lt;/i&gt;6 Gene and Risk of Relapsing-Remitting Multiple Sclerosis (RRMS) in Isfahan Population

“…IL6-174 CC genotype occurred more than twice as often for patients (29.4%) as for healthy controls (12.4%) (P < 0.00001, OR = 2.86, 95% CI 1.7 -4.9). Another study by Sfrentcornateanu et al [12], carried out on IL-6 promoter polymorphism in systemic sclerosis patients, showed that the GG homozygosis was found to be associated with a higher degree of illness activity and disability in systemic sclerosis patients. In a study of systemic lupus erythematosus (SLE) patients carried out on rs1800795 polymorphism by Chua et al [11], significant association was observed at homozygous G genotype in SLE patients.…”

Targeting Systemic Sclerosis from Pathogenic Mechanisms to Clinical Manifestations: Why IL-6?

“…This genetic polymorphism of IL-6 was correlated only with the presence of gastrointestinal manifestations, not with skin and lung damage [ 50 ]. Other data obtained after studying 20 cases with SS support the link between IL-6 polymorphism, especially the homozygous GG form, and an active and disabling disease [ 51 ].…”