Svikle Zane, Paramonova Natalia, Siliņš Emīls, Pahirko Leonora, Zariņa Līga, Baumane Kristīne, Petrovski Goran, Sokolovska Jelizaveta
Faculty of Medicine, University of Latvia, Jelgavas Street 3, LV 1004 Riga, Latvia.
Institute of Biology, University of Latvia, Jelgavas Street 1, LV 1004 Riga, Latvia.
Biomedicines. 2024 Jun 18;12(6):1354. doi: 10.3390/biomedicines12061354.
We explored differences in the DNA methylation statuses of , , , and gene promoter regions in patients with type 1 diabetes and different diabetic retinopathy (DR) stages. Study subjects included individuals with no DR (NDR, = 41), those with non-proliferative DR (NPDR, = 27), and individuals with proliferative DR or those who underwent laser photocoagulation (PDR/LPC, = 46). DNA methylation was determined by Zymo OneStep qMethyl technique. The methylation of (NDR 5.9 (3.9-8.7) %, NPDR 4.5 (3.8-5.7) %, PDR/LPC 6.6 (4.7-10.7) %, = 0.003) and (NDR 2.2 (1.9-3.7) %, NPDR 2.2 (1.9-3.0) %, PDR/LPC 3.2 (2.5-7.1) %, < 0.01) differed across the groups. Consistent correlations were observed between the methylation levels of and in all study groups. DNA methylation levels of , , and genes were positively correlated with the duration of diabetes, HbA1c, and albuminuria in certain study groups. Univariate regression models revealed a significant association between the methylation level z-scores of , , and and severe DR (: OR = 1.96 (1.15; 3.33), = 0.013; : OR = 1.90 (1.14; 3.16), = 0.013; : OR = 3.19 (1.26; 8.06), = 0.014). remained significantly associated with DR in multivariate analysis. Our findings suggest significant associations between the severity of DR and the DNA methylation levels of the genes , , and , but not gene.
我们探究了1型糖尿病患者以及不同糖尿病视网膜病变(DR)阶段患者中,[具体基因1]、[具体基因2]、[具体基因3]和[具体基因4]基因启动子区域的DNA甲基化状态差异。研究对象包括无DR的个体(NDR,n = 41)、非增殖性DR个体(NPDR,n = 27)以及增殖性DR个体或接受激光光凝治疗的个体(PDR/LPC,n = 46)。DNA甲基化通过Zymo OneStep qMethyl技术测定。[具体基因1](NDR为5.9(3.9 - 8.7)%,NPDR为4.5(3.8 - 5.7)%,PDR/LPC为6.6(4.7 - 10.7)%,P = 0.003)和[具体基因2](NDR为2.2(1.9 - 3.7)%,NPDR为2.2(1.9 - 3.0)%,PDR/LPC为3.2(2.5 - 7.1)%,P < 0.01)的甲基化在各研究组间存在差异。在所有研究组中,均观察到[具体基因1]和[具体基因2]甲基化水平之间存在一致的相关性。在某些研究组中,[具体基因3]、[具体基因4]和[具体基因5]基因的DNA甲基化水平与糖尿病病程、糖化血红蛋白(HbA1c)和蛋白尿呈正相关。单因素回归模型显示,[具体基因3]、[具体基因4]和[具体基因5]的甲基化水平z评分与严重DR之间存在显著关联([具体基因3]:比值比(OR)= 1.96(1.15;3.33),P = 0.013;[具体基因4]:OR = 1.90(1.14;3.16),P = 0.013;[具体基因5]:OR = 3.19(1.26;8.06),P = 0.014)。在多因素分析中,[具体基因5]与DR仍显著相关。我们的研究结果表明,DR的严重程度与[具体基因3]、[具体基因4]和[具体基因5]基因的DNA甲基化水平之间存在显著关联,但与[具体基因1]基因无关。