Institute of Rheumatology, Belgrade, Serbia.
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Clin Rheumatol. 2018 Sep;37(9):2447-2454. doi: 10.1007/s10067-018-4163-6. Epub 2018 Jun 8.
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.
系统性硬化症(SSc)的遗传易感性尚未完全揭示。白细胞介素-6(IL-6)是 SSc 中 T 细胞增殖和纤维化事件的介质。IL-6 中的多态性被发现对 SSc 的发病易感性很重要。我们旨在评估 SSc 患者和健康对照者中 IL-6 基因 -174C/G 多态性的频率,以及与疾病表现的相关性。在病例对照研究中,纳入了 102 例 SSc 患者和 93 名对照者。采用 PCR-RFLP 法对 IL-6 基因启动子变异 -174C/G 进行基因分型。对 50 例患者和 13 名健康对照者的不同 IL-6 基因型进行 qRT-PCR 测定 IL-6 基因的表达水平。我们使用 UCLA GIT 2.0 问卷评估 SSc 患者的胃肠道受累情况。与健康对照组相比,SSc 患者的 IL-6 基因表达水平显著升高(p<0.05)。与携带 G 等位基因的患者相比,IL-6 基因的 C 等位基因携带者的 IL-6 基因表达水平更高(95.8 比 41.2,p<0.05),GIT 总分更高(0.85 比 0.5,p<0.05),扩张量表评分更高(1.4±0.9 比 0.78±0.8,p=0.05)。患者和对照组之间在基因型分布和等位基因频率方面无显著差异。IL6 基因的表达在 SSc 病程中差异显著。IL-6 基因变异 -174C/G(存在 C 等位基因)与 SSc 患者更高的 IL-6 基因表达和更大的 GIT 损害相关。