PDF(Pubmed)
Abstract：
We explored differences in the DNA methylation statuses of PSMA6, PSMB5, HIF1A, and KEAP1 gene promoter regions in patients with type 1 diabetes and different diabetic retinopathy (DR) stages. Study subjects included individuals with no DR (NDR, n = 41), those with non-proliferative DR (NPDR, n = 27), and individuals with proliferative DR or those who underwent laser photocoagulation (PDR/LPC, n = 46). DNA methylation was determined by Zymo OneStep qMethyl technique. The methylation of PSMA6 (NDR 5.9 (3.9-8.7) %, NPDR 4.5 (3.8-5.7) %, PDR/LPC 6.6 (4.7-10.7) %, p = 0.003) and PSMB5 (NDR 2.2 (1.9-3.7) %, NPDR 2.2 (1.9-3.0) %, PDR/LPC 3.2 (2.5-7.1) %, p < 0.01) differed across the groups. Consistent correlations were observed between the methylation levels of HIF1A and PSMA6 in all study groups. DNA methylation levels of PSMA6, PSMB5, and HIF1A 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 PSMA6, PSMB5, and HIF1A and severe DR (PSMA6: OR = 1.96 (1.15; 3.33), p = 0.013; PSMB5: OR = 1.90 (1.14; 3.16), p = 0.013; HIF1A: OR = 3.19 (1.26; 8.06), p = 0.014). PSMB5 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 PSMA6, PSMB5, and HIF1A, but not KEAP1 gene.
摘要：
我们探索了PSMA6，PSMB5，HIF1A，1型糖尿病和不同糖尿病视网膜病变（DR）分期患者的KEAP1基因启动子区。研究对象包括无DR的个体(NDR，n=41),那些具有非增殖性DR(NPDR，n=27),和患有增生性DR的个体或接受激光光凝的个体(PDR/LPC，n=46）。通过ZymoOneStepqMethyl技术确定DNA甲基化。PSMA6的甲基化（NDR5.9（3.9-8.7）％，NPDR4.5（3.8-5.7）%，PDR/LPC6.6（4.7-10.7）%，p=0.003）和PSMB5（NDR2.2（1.9-3.7）%，NPDR2.2（1.9-3.0）%，PDR/LPC3.2(2.5-7.1)%,p<0.01）各组之间存在差异。在所有研究组中HIF1A和PSMA6的甲基化水平之间观察到一致的相关性。PSMA6、PSMB5、HIF1A基因DNA甲基化水平与糖尿病病程呈正相关,HbA1c,某些研究组的蛋白尿。单变量回归模型显示PSMA6，PSMB5和HIF1A的甲基化水平z评分与严重DR之间存在显着关联（PSMA6：OR=1.96（1.15;3.33），p=0.013；PSMB5：OR=1.90（1.14；3.16），p=0.013;HIF1A:OR=3.19(1.26;8.06),p=0.014)。在多变量分析中，PSMB5仍然与DR显著相关。我们的研究结果表明，DR的严重程度与PSMA6，PSMB5和HIF1A基因的DNA甲基化水平之间存在显着关联。但不是KEAP1基因。
