Association between the -174 C/G polymorphism in the interleukin-6 (IL-6) gene and gastrointestinal involvement in patients with systemic sclerosis

Abstract

Genetic predisposition to systemic sclerosis (SSc) has still not been fully revealed. Interleukin-6 (IL-6) is a mediator of T cell proliferation and fibrotic events in SSc. Polymorphisms in the IL-6 are found to be important in susceptibility to development of SSc. We aimed to assess the frequency of -174 C/G of IL-6 gene polymorphism in SSc patients and healthy controls, as well as correlation with disease manifestations. In the case-control study, 102 patients with SSc and 93 controls were included. PCR-RFLP method was performed for genotyping promotor variants -174 C/G of IL-6 gene. The expression level of IL-6 was determined by qRT-PCR on subset of 50 patients and 13 healthy controls with different IL-6 genotypes. We used UCLA GIT 2.0 questionnaire to assess gastrointestinal involvement in SSc patients. The expression level of IL-6 gene was significantly higher in patients with SSc in comparison with healthy controls (p < 0.05). Carriers of C-allele of IL-6 gene compared to those with G allele, showed higher expression of IL-6 gene (95.8 vs. 41.2, p < 0.05), higher GIT total score (0.85 vs. 0.5, p < 0.05) and higher distension scale score (1.4 ± 0.9 vs. 0.78 ± 0.8, p = 0.05). No significant differences in genotype distribution and allele frequency were observed between patients and controls. The expression of IL6 gene varies significantly during the course of SSc. The IL-6 gene variant -174 C/G (presence of C-allele) is associated with higher IL-6 gene expression and greater GIT impairment in patients with SSc.

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

“…In addition to lung damage, 90% of SS patients also have gastrointestinal involvement (GI) [ 85 ], which is the 3rd leading cause of death [ 86 ]. GI impairment is associated with a marked disability and a decreased quality of life in SS patients, leading to reduced survival [ 86 , 87 ]. IL-6 gene polymorphism increases disease susceptibility, being associated with different clinical manifestations [ 49 ].…”

Dysbiosis and Gut Microbiota Modulation in Systemic Sclerosis

“…The heterogeneous disease presentation reflects a complex pathogenesis, with multiple pathways involved 7 . Indeed, several biological mechanisms have been described, none of which fully explain the wide spectrum of GI manifestations 18–24 …”

“…7 Indeed, several biological mechanisms have been described, none of which fully explain the wide spectrum of GI manifestations. [18][19][20][21][22][23][24]…”

Can Pharmacogenetic Variants in TPMT, MTHFR and SLCO1B1 Genes Be Used as Potential Markers of Outcome Prediction in Systemic Sclerosis Patients?

“…Other than aforementioned ILD and PH, common symptoms of disease progression are digestive disorders, skin thickening, appearance of digital ulcers etc. Many of these symptoms are associated with the presence of particular genetic variants, for instance, allele C in IL-6 gene variant -174C/G is associated with severe gastrointestinal complications [3]. What is more, frequency and mortality of patients with SSc depend on patients' sex and ancestry.…”