Basavaraju Preethi, Moorthi Puthamohan Vinayaga, Meyyazhagan Arun, Devaraj Ilakkiyapavai, Babu Kavipriya, Panza Emanuele, Orlacchio Antonio
Biomaterial and Nano-materials Laboratory, Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore, Tamil Nadu, India.
Dipartimento di Medicina e Chirurgia, Università di Perugia, Piazza L. Severi - Edificio B, Piano 1, Sant'Andrea delle Fratte, Perugia, 06132, Italy.
Acta Diabetol. 2025 Apr;62(4):487-497. doi: 10.1007/s00592-024-02374-2. Epub 2024 Oct 17.
Diabetic nephropathy (DN) is a grave complication and the most common renal dysfunction of diabetes mellitus. Genetic factors, including Apolipoprotein E (APOE) isoforms, have been implicated in the pathogenesis of DN.
A total of 577 type 2 Diabetes mellitus subjects were categorized into diabetes non-nephropathic (Controls: n = 321), diabetes nephropathic (DN: n = 256) groups. Demographic, clinical, and biochemical parameters including age, BMI, lipid profiles (TC, LDL-C, HDL-C, TG), glucose metabolism (plasma glucose, HbA1c, serum insulin), renal function (UACR, PCR), and blood pressure (SBP, DBP) were assessed. APOE variant frequencies were determined using restriction fragment length polymorphism (RFLP) analysis, validated against Hardy-Weinberg equilibrium (HWE), and statistically correlated with each clinical and biochemical parameter.
The DN group had an increased prevalence of hypertension, fatty liver, and dyslipidemia compared to the Control group. Biochemical analyses revealed elevated levels of TC (213.41 mg/dL vs. 189.32 mg/dL), LDL-C (134.46 mg/dL vs. 107.56 mg/dL), and reduced HDL-C (58.13 mg/dL vs. 65.32 mg/dL) in DN cases compared to Controls (all p < 0.0001). The APOE variants distribution showed a significant increase in E2 allele frequency (69.1% vs. 15.3%) and corresponding homozygous genotype (E2/2: 42.2% vs. 5.6%) in DN cohorts.
The study found a higher frequency of E2 allele in the DN group compared to Controls, though no statistically significant risk of DN was linked to this allele. The results suggest a potential association for APOE polymorphisms, requiring broader studies to clarify the role of APOE polymorphisms in DN susceptibility.
糖尿病肾病(DN)是一种严重的并发症,也是糖尿病最常见的肾功能障碍。包括载脂蛋白E(APOE)异构体在内的遗传因素与DN的发病机制有关。
将总共577例2型糖尿病患者分为糖尿病非肾病组(对照组:n = 321)和糖尿病肾病组(DN组:n = 256)。评估人口统计学、临床和生化参数,包括年龄、体重指数、血脂谱(总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酯)、糖代谢(血糖、糖化血红蛋白、血清胰岛素)、肾功能(尿白蛋白肌酐比值、蛋白质肌酐比值)和血压(收缩压、舒张压)。使用限制性片段长度多态性(RFLP)分析确定APOE变体频率,根据哈迪-温伯格平衡(HWE)进行验证,并与每个临床和生化参数进行统计学关联。
与对照组相比,DN组高血压、脂肪肝和血脂异常的患病率更高。生化分析显示,与对照组相比,DN患者的总胆固醇(213.41mg/dL对189.32mg/dL)、低密度脂蛋白胆固醇(134.46mg/dL对107.56mg/dL)水平升高,高密度脂蛋白胆固醇(58.13mg/dL对65.32mg/dL)降低(所有p < 0.0001)。APOE变体分布显示,DN队列中E2等位基因频率(69.1%对15.3%)和相应的纯合基因型(E2/2:42.2%对5.6%)显著增加。
该研究发现,与对照组相比,DN组中E2等位基因的频率更高,尽管该等位基因与DN没有统计学上的显著风险关联。结果表明APOE多态性可能存在关联,需要更广泛的研究来阐明APOE多态性在DN易感性中的作用。