Izakovicova Pavla, Slezakova Simona, Deissova Tereza, Poskerova Hana, Borilova Linhartova Petra, Dusek Ladislav, Kankova Katerina, Izakovicova Holla Lydie
Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Clinic of Stomatology, Faculty of Medicine, Institution Shared with St. Anne's University Hospital, Masaryk University, Brno, Czech Republic.
J Diabetes Investig. 2025 Aug;16(8):1463-1472. doi: 10.1111/jdi.70073. Epub 2025 May 29.
The pathogenesis of diabetes mellitus (DM) and its complications has been previously linked to elevated levels of interleukin-6 (IL-6); IL-6 triggers intracellular pathways through interaction with the IL-6 receptor (IL-6R). This study aimed to determine the association of single nucleotide polymorphisms (SNPs) IL-6 -597G/A (rs1800797), -572G/C (rs1800796), -174G/C (rs1800795), its receptor (IL-6R) Asp358Ala (+48892A/C, rs2228145) and DM or its complications in the Czech population.
In total, 669 subjects participated in this case-control study, including 167 controls, 119 patients with type 1 DM (T1DM), and 383 patients with type 2 DM (T2DM). The subjects were monitored for glycemia, glycated hemoglobin, lipid profile, glomerular filtration rate (GFR), and common complications, such as diabetic nephropathy (DN), retinopathy (DR), (poly)neuropathy (DPN), and periodontitis (P).
Frequencies of the IL-6 and IL-6R alleles or genotypes, and IL-6 haplotypes were similar between the controls and the patients with T1DM or T2DM (P > 0.05). However, lower values of GFR were observed in diabetic patients with IL-6 -174CC homozygotes compared to other (CG and GG) genotypes (P ≤ 0.05). In addition, the IL-6R Asp358Ala variant was associated with DN (P = 0.031, OR = 1.74, 95% CI: 1.05-2.89). After subclassification according to the type of DM, the significant association of the IL-6R polymorphism with DN was only found in T1DM (P = 0.013, OR = 2.90, 95% CI: 1.25-6.71).
This study implies a significant relationship between the IL-6R Asp358Ala polymorphism and DN in Czech T1DM patients.
糖尿病（DM）及其并发症的发病机制此前一直与白细胞介素 -6（IL -6）水平升高有关；IL -6通过与白细胞介素 -6受体（IL -6R）相互作用触发细胞内信号通路。本研究旨在确定单核苷酸多态性（SNP）IL -6 -597G/A（rs1800797）、-572G/C（rs1800796）、-174G/C（rs1800795）及其受体（IL -6R）Asp358Ala（+48892A/C，rs2228145）与捷克人群中DM或其并发症之间的关联。
共有669名受试者参与了这项病例对照研究，包括167名对照者、119名1型糖尿病（T1DM）患者和383名2型糖尿病（T2DM）患者。对受试者进行血糖、糖化血红蛋白、血脂谱、肾小球滤过率（GFR）以及常见并发症的监测，如糖尿病肾病（DN）、视网膜病变（DR）、（多）神经病变（DPN）和牙周炎（P）。
对照组与T1DM或T2DM患者之间，IL -6和IL -6R等位基因或基因型以及IL -6单倍型的频率相似（P＞0.05）。然而，与其他（CG和GG）基因型相比，IL -6 -174CC纯合子的糖尿病患者GFR值较低（P≤0.05）。此外，IL -6R Asp358Ala变异与DN相关（P = 0.031，OR = 1.74，95%CI：1.05 - 2.89）。根据DM类型进行亚组分析后，仅在T1DM中发现IL -6R多态性与DN存在显著关联（P = 0.013，OR = 2.90，95%CI：1.25 - 6.71）。
本研究表明在捷克T1DM患者中IL -6R Asp358Ala多态性与DN之间存在显著关联。
