Istanbul University, Aziz Sancar Institute for Experimental Medicine, Department of Genetics, Istanbul, Turkey; Istanbul University, Graduate School of Health Sciences, Istanbul, Turkey.
Ufuk University, Faculty of Medicine, Department of Cardiology, Ankara, Turkey.
J Diabetes Complications. 2022 Jan;36(1):108078. doi: 10.1016/j.jdiacomp.2021.108078. Epub 2021 Oct 15.
Coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) are important and increasing public health problems. This study aimed to identify the impact of APOE and CLU gene polymorphisms on the prevalence of both diseases, along with the effect of these polymorphisms on lipid profile and glucose metabolism.
736 CAD patients (≥50 stenosis) and 549 non-CAD subjects (≤30 stenosis) were genotyped for APOE (rs429358 and rs7412) and CLU (rs11136000) gene polymorphisms using hydrolysis probes in real-time PCR. Blood samples of the individuals were drawn before coronary angiography and biochemical analyses were done. The associations between the polymorphisms and the selected parameters were assessed using statistical analysis.
In this study, the ε2 and ε4 isoforms of apoE were associated with serum lipid levels and TC/HDL-C and LDL-C/HDL-C ratios in analysis adjusted for several confounders and in crude analysis. It was observed that CLU T allele carrier non-CAD subjects had lower glycosylated hemoglobin levels. Furthermore, the effects of APOE and CLU polymorphisms were assessed on CAD and T2DM presence. In crude and multiple logistic regression analyses, the ε2 isoform carriers had a lower risk for CAD complexed with T2DM. When the combinational effects of APOE and CLU polymorphisms were examined, the ε2 and T allele carriers had decreased risk for CAD complexed with T2DM compared to non-carriers.
In conclusion, the combination of APOE and CLU polymorphisms is associated with CAD-DM status along with the APOE ε2 isoform by itself, and the apoE isoforms are strongly associated with serum lipid levels.
冠心病(CAD)和 2 型糖尿病(T2DM)是重要且日益严重的公共卫生问题。本研究旨在确定 APOE 和 CLU 基因多态性对这两种疾病的患病率的影响,以及这些多态性对血脂谱和葡萄糖代谢的影响。
使用实时 PCR 水解探针对 736 名 CAD 患者(≥50%狭窄)和 549 名非 CAD 患者(≤30%狭窄)进行 APOE(rs429358 和 rs7412)和 CLU(rs11136000)基因多态性的基因分型。个体的血液样本在冠状动脉造影前采集,并进行生化分析。使用统计分析评估多态性与所选参数之间的关系。
在本研究中,apoE 的 ε2 和 ε4 同工型与血清脂质水平以及 TC/HDL-C 和 LDL-C/HDL-C 比值相关,在经过多项混杂因素调整的分析和未调整的分析中均如此。观察到 CLU T 等位基因携带者的非 CAD 患者糖化血红蛋白水平较低。此外,还评估了 APOE 和 CLU 多态性对 CAD 和 T2DM 存在的影响。在未调整和多元逻辑回归分析中,ε2 同工型携带者发生 CAD 合并 T2DM 的风险较低。当检查 APOE 和 CLU 多态性的组合效应时,与非携带者相比,ε2 和 T 等位基因携带者发生 CAD 合并 T2DM 的风险降低。
总之,APOE 和 CLU 多态性的组合与 CAD-DM 状态相关,APOE ε2 同工型本身也是如此,apoE 同工型与血清脂质水平密切相关。