白细胞介素-18 启动子-137 G/C 多态性(rs187238)与 2 型糖尿病患者肾功能和心血管疾病的生化标志物相关。

Interleukin-18 promoter -137 G/C polymorphism (rs187238) is associated with biochemical markers of renal function and cardiovascular disease in type 2 diabetes patients.

机构信息

Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza, Ceará, Brazil.

出版信息

Clin Biochem. 2020 Jun;80:1-7. doi: 10.1016/j.clinbiochem.2020.03.011. Epub 2020 Mar 21.

DOI:10.1016/j.clinbiochem.2020.03.011

PMID:32209332

Abstract

BACKGROUND

Interleukin-18 (IL-18), a proinflammatory and proatherogenic cytokine, has been associated with type 2 diabetes, metabolic syndrome, stroke and coronary artery disease. Some studies have indicated that the IL-18 promoter -137 G/C polymorphism seems to be associated with changes in the IL-18 expression and may contribute to the development of cardiovascular disease (CVD). The aim of this study was to evaluate the association between -137 G/C polymorphism and the levels of IL-18, biochemical markers for cardiovascular disorders, anthropometric profile and cardiovascular disease in Brazilian patients with type 2 diabetes (T2DM).

DESIGN & METHODS: Study subjects comprised 125 T2DM patients undergoing follow-up at a reference endocrinology service in northeastern Brazil. The -137G/C polymorphism in the IL-18 gene and serum IL-18 levels were determined by using allele-specific polymerase chain reaction (PCR) and enzyme-linked immune assay (ELISA), respectively. The anthropometric parameters were assessed using a Body Composition Monitor with Scale, and the laboratory data were measured using an automatic analyzer as well as spectrophotometric analysis.

RESULTS

The genotype distribution of IL-18 -137 G/C genetic polymorphism was significantly different among T2DM patients with and without CVD. The results show an association between the CC genotype of -137G/C polymorphism and CVD in T2DM patients (p < 0.001). Serum levels of IL-18 were significantly higher in CC carriers (843.1 pg/mL) compared with GG or GC carriers (303.6 pg/mL and 292.0 pg/mL, respectively). In addition, the present study showed that carriers of the CC genotype also had significantly higher concentrations of creatinine and albuminuria than carriers of the GG or GC genotypes (p < 0.05 in both).

CONCLUSION

These results suggest that Brazilian T2DM patients with the CC genotype seem to show a predisposition to CVD, as well as an elevation in markers of renal function.

摘要

背景

白细胞介素-18（IL-18）是一种促炎和促动脉粥样硬化细胞因子，与 2 型糖尿病、代谢综合征、中风和冠状动脉疾病有关。一些研究表明，IL-18 启动子-137 G/C 多态性似乎与 IL-18 表达的变化有关，并可能导致心血管疾病（CVD）的发生。本研究旨在评估-137 G/C 多态性与白细胞介素-18 水平、心血管疾病生化标志物、人体测量学特征和巴西 2 型糖尿病（T2DM）患者心血管疾病之间的关系。

设计与方法

研究对象为在巴西东北部一家内分泌学参考服务机构接受随访的 125 例 T2DM 患者。采用等位基因特异性聚合酶链反应（PCR）和酶联免疫吸附试验（ELISA）分别检测 IL-18 基因-137G/C 多态性和血清 IL-18 水平。采用体成分监测仪和 Scale 评估人体测量学参数，采用自动分析仪和分光光度分析测量实验室数据。

结果

IL-18-137G/C 遗传多态性的基因型分布在 T2DM 合并或不合并 CVD 患者之间存在显著差异。结果表明，-137G/C 多态性 CC 基因型与 T2DM 患者 CVD 之间存在关联（p<0.001）。CC 携带者的血清 IL-18 水平显著高于 GG 或 GC 携带者（分别为 843.1pg/mL、303.6pg/mL 和 292.0pg/mL）。此外，本研究还显示，CC 基因型携带者的肌酐和蛋白尿浓度也显著高于 GG 或 GC 基因型携带者（p<0.05）。