Lima Christiane Mayrhofer Grocoske de, de Melo Rafaela Cirillo, Souza Nathalia Marçallo Peixoto, Silva Paula Rothbarth, Aguiar Dayane Ferreira, Ferreira Luana Mota, Volanski Waldemar, Picheth Geraldo, Rego Fabiane Gomes de Moraes, Sari Marcel Henrique Marcondes
Graduate Program in Pharmaceutical Sciences, Department of Clinical Analysis, Federal University of Paraná, Curitiba 80210-170, PR, Brazil.
Pharmacy Course, Federal University of Paraná, Curitiba 80210-170, PR, Brazil.
Biomedicines. 2025 Sep 11;13(9):2242. doi: 10.3390/biomedicines13092242.
: Type 2 diabetes mellitus (T2DM) is a chronic and multifactorial metabolic disorder associated with genetic and environmental factors. Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis and vascular homeostasis, and genetic polymorphisms in the signaling pathway have been linked to the T2DM development, progression, and complications. This scoping review investigated the association between gene and receptors single-nucleotide polymorphisms (SNPs) and susceptibility to T2DM and vascular complications. : A thorough systematic review was performed utilizing scientific databases (PubMed, Web of Science, and Scopus) in March 2025. From an initial pool of 796 records, 59 relevant articles were selected for inclusion in the analysis. The most frequently studied SNPs were rs2010963 (31/59), rs699947 (16/59), rs3025039 (15/59), rs833061 (11/59), rs1570360 (7/59) in the gene and rs2071559(6/59) in . The studies include a diverse range of ethnic groups, including Asian, European and Middle Eastern populations. The main complications associated with these SNPs were microvascular conditions such as diabetic retinopathy (DR) (49/59), diabetic neuropathy (DPN) (6/59), diabetic nephropathy (DNP) (2/59), and as well as macrovascular complications including diabetic foot ulcers (DFU) (10/59). The results revealed that these polymorphisms, particularly rs3025039 and rs2010963, were more consistently associated with microvascular complications such as DR rather than with T2DM itself. The C allele of rs2010963 was associated with increased risk of DR in Indian populations, while no such association was observed in European. Similarly, the T allele of rs3025039 conferred protection against DPN in a Chinese population but was associated with higher DR risk in an Indian study, suggesting that the same allele may play distinct roles depending on ethnic background and clinical phenotype. : signaling pathway genetic polymorphisms demonstrate potential as biomarkers for diabetic complications, especially microvascular outcomes. The findings suggest a genetic basis for differences in complications of T2DM. Future studies should investigate relevant SNPs across diverse ethnic groups to better understand genetic risks associated with the disease and its vascular complications.
2型糖尿病（T2DM）是一种与遗传和环境因素相关的慢性多因素代谢紊乱疾病。血管内皮生长因子（VEGF）在血管生成和血管稳态中起关键作用，该信号通路中的基因多态性与T2DM的发生、发展及并发症有关。本综述探讨了该基因和受体单核苷酸多态性（SNP）与T2DM易感性及血管并发症之间的关联。：2025年3月利用科学数据库（PubMed、Web of Science和Scopus）进行了全面的系统综述。从最初的796条记录中，筛选出59篇相关文章纳入分析。该基因中研究最频繁的SNP有rs2010963（59篇中的31篇）、rs699947（59篇中的16篇）、rs3025039（59篇中的15篇）、rs833061（59篇中的11篇）、rs1570360（59篇中的7篇），受体中的rs2071559（59篇中的6篇）。这些研究涵盖了多种族群体，包括亚洲、欧洲和中东人群。与这些SNP相关的主要并发症包括微血管病变，如糖尿病视网膜病变（DR）（59篇中的49篇）、糖尿病神经病变（DPN）（59篇中的6篇）、糖尿病肾病（DNP）（59篇中的2篇），以及大血管并发症，如糖尿病足溃疡（DFU）（59篇中的10篇）。结果显示，这些多态性，尤其是rs3025039和rs2010963，与DR等微血管并发症的关联更为一致，而非与T2DM本身。rs2010963的C等位基因与印度人群中DR风险增加相关，而在欧洲人群中未观察到这种关联。同样，rs3025039的T等位基因在中国人群中对DPN有保护作用，但在一项印度研究中与较高的DR风险相关，这表明同一等位基因可能因种族背景和临床表型而发挥不同作用。：该信号通路基因多态性显示出作为糖尿病并发症生物标志物的潜力，尤其是微血管病变结局。这些发现提示了T2DM并发症差异的遗传基础。未来研究应在不同种族群体中研究相关SNP，以更好地了解与该疾病及其血管并发症相关的遗传风险。
