Study on the correlation between promoter methylation of ABCG1 gene and the onset of diabetic kidney disease

Han Mengying; Wang Xin; Zhang Jingyuan; Li Yanan; Bao Lier; Wang Bo

doi:10.3969/j.issn.1671-6450.2026.03.002

Abstract：Objective To explore the relationship between promoter methylation of ATP-binding cassette transporter G1(ABCG1)gene and the onset of diabetic kidney disease(DKD).Methods A retrospective analysis was conducted on the test results of 60 blood samples collected from the Affiliated Hospital of Inner Mongolia Medical University between Decem-ber 2023 and December 2024.The samples were divided into three groups:20 patients with DKD(DKD group),20 patients with type 2 diabetes mellitus(DM group),and 20 healthy individuals(healthy control group).Clinical data and biochemical in-dicators of each group were collected.The methylation level of the ABCG1 gene promoter in serum was detected using the bi-sulfite sequencing method.Differences in the aforementioned indicators among the three groups were compared.Logistic re-gression analysis and receiver operating characteristic(ROC)curve analysis were applied to explore the correlation between the methylation level of the ABCG1 gene promoter and the occurrence of DKD in patients with type 2 diabetes mellitus.Re-sults Compared with the healthy control group,the levels of HbA1c and FPG were increased,and HDL was decreased in both the DM group and the DKD group(F/P=65.357/＜0.001,33.140/＜0.001,11.634/＜0.001).In the DKD group,LDL,SCr,and BUN were increased,and eGFR was decreased(t/P=3.125/0.003,3.186/0.003,3.317/0.002,-4.348/＜0.001).Compared with the DM group,SCr and BUN were increased,and eGFR was decreased in the DKD group(t/P=3.047/0.004,2.534/0.016,3.353/0.002).There were no statistically significant differences in TC,TG,LDL,HDL,HbA1c,and FPG between the DM group and the DKD group(all P＞0.05).The methylation levels of the ABCG1 gene promoter region in the three groups de-creased progressively,and the difference was statistically significant(x2=7.381,P＜0.05).Compared with the healthy control group,ABCG1 promoter methylation in the DKD group was significantly decreased(x2=6.160,P＜0.05),while there was no statistically significant difference in ABCG1 methylation in the DM group(x2=1.938,P＞0.05).In addition,when comparing the DM group with the DKD group,there was no statistically significant difference in ABCG1 promoter methylation(x2=2.297,P＞0.05).Elevated LDL and decreased eGFR were independent risk factors for the development of DKD in patients with type 2 diabetes,while increased methylation level of the ABCG1 gene promoter was a protective factor[OR(95％CI)=10.738(1.139-101.238),0.818(0.694-0.964),0.001(0.000-0.195)].The AUCs for predicting the occurrence of DKD in patients with type 2 diabetes using LDL,eGFR,ABCG1 gene promoter methylation,and their combination were 0.712,0.835,0.650,and 0.951,respectively.The combination of the three was superior to each individual predictor(differences were compared using the DeLong method)(Z/P=3.353/0.001,1.949/0.041,5.401/＜0.001).Conclusion Demethylation of the ABCG1 gene promoter may be involved in the pathogenesis of DKD,and detection of the methylation level of the ABCG1 gene promoter may be helpful for the diagnosis of DKD.