Circulating microRNA-194 levels in Chinese patients with diabetic kidney disease: a case-control study

Ning Ma; Ning Xu; Dong Yin; Ping Zheng; Weiwei Liu; Guofeng Wang; Yuan Hui; Jiping Zhang; Guanjun Han; Chuanhui Yang; Yiting Chen; Xingbo Cheng; Ming Cheng

doi:10.1177/20420188211049615

Circulating microRNA-194 levels in Chinese patients with diabetic kidney disease: a case-control study

Ther Adv Endocrinol Metab. 2021 Oct 15:12:20420188211049615. doi: 10.1177/20420188211049615. eCollection 2021.

Authors

Ning Ma¹, Ning Xu¹, Dong Yin¹, Ping Zheng¹, Weiwei Liu¹, Guofeng Wang¹, Yuan Hui¹, Jiping Zhang¹, Guanjun Han¹, Chuanhui Yang¹, Yiting Chen², Xingbo Cheng³, Ming Cheng⁴

Affiliations

¹ Department of Endocrinology and Metabolism, The First People's Hospital of Lianyungang, Lianyungang, China.
² Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, Suzhou, China.
³ Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou 215006, Jiangsu, China.
⁴ School of Rail Transportation, Soochow University, 1 Shizi Road, Suzhou 215006, Jiangsu, China.

Abstract

Objective: MicroRNAs (miRNAs) regulate gene expression and are involved in diabetic kidney disease (DKD) pathogenesis. We investigated circulating miRNA-194 levels as a biomarker of DKD prevalence and incidence, and the relationship between miRNA-194 and CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP).

Methods: We recruited 136 type-2 diabetes mellitus (T2DM) patients at the First People's Hospital of Lianyungang and 127 healthy individuals. Circulating miRNA-194 and CHOP levels were measured using quantitative reverse transcription qRT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Anthropometric and biochemistry measurements were also made.

Results: T2DM patients showed higher circulating miRNA-194 (p = 0.029) and lower circulating CHOP (p < 0.001) levels than controls. Circulating miRNA-194 levels were significantly higher in T2DM patients with a microalbumin/creatinine ratio (UmALB/Cr) ⩾ 300 mg/g (p < 0.001). In addition, there were significant intergroup differences in the circulating CHOP concentrations (p = 0.005). Bivariate analysis revealed that circulating miR-194 levels were negatively correlated with alpha-fetoprotein and CHOP levels (r = -0.222, -0.301; p = 0.018, 0.001, respectively), but positively correlated with fasting glucose, UmALB/Cr, Cr, Cystatin C, quantitative insulin check index (QUICKI) (r = 0.193, 0.446, 0.260, 0.339, and 0.250, respectively; p = 0.036, <0.001, 0.005, <0.001, and 0.006, respectively), particularly UmALB/Cr and Cystatin C (p < 0.001). Logistic regression analysis after adjusting for covariates associated with UmALB/Cr identified duration of T2DM, systolic blood pressure, Cr, estimated glomerular filtration rate, and waist circumference as independent factors associated with T2DM patients with UmALB/Cr > 300 (p = 0.030, 0.013, <0.001, <0.001, and 0.031, respectively).

Conclusion: Circulating miRNA-194 levels could be a novel biomarker for DKD.

Keywords: CCAAT/enhancer binding protein homology protein (CHOP); diabetic kidney disease (DKD); endoplasmic reticulum stress; microRNA-194; type-2 diabetes mellitus.