Correlation analysis of circRNA-ZNF532 and circRNA-HIPK3 with diabetic retinopathy

doi:10.11958/20230048

Abstract

Abstract:

Objective To investigate the correlation between circrNa-Zinc finger protein 532 (ZNF532), circrNa-homologous domain interaction protein kinase-3 (HIPK3) and diabetic retinopathy (DR). Methods A total of 109 patients with DR (DR group), 110 patients with simple diabetes (DM group) and 65 healthy volunteers (control group) were selected from our hospital from October 2020 to October 2022. Serum circRNA-ZNF532 and circRNA-HIPK3 expression levels were detected by real-time quantitative polymerase chain reaction (RT-PCR), and serum vascular endothelial growth factor (VEGF), interleukin (IL) -1β, tumor necrosis factor (TNF) -α and IL-6 levels were detected by enzyme-linked immunosoradsorption assay. The correlation between serum circRNA-ZNF532 and circRNA-HIPK3 expression and serum levels of VEGF, IL-1β, TNF-α and IL-6 were analyzed by Pearson method. Univariate Logistic regression analysis and multivariate Logistic regression analysis were used for DR risk factors, and receiver operating characteristic curve (ROC) was used for analysis of circRNA-ZNF532 and circRNA-HIPK3 diagnostic value of DR. Results Serum expressions of circRNA-ZNF532 and circRNA-HIPK3 and levels of VEGF, IL-1β, TNF-α and IL-6 were significantly higher in the DR group than those in the DM group and the control group (P<0.05). Serum circRNA-ZNF532 and circRNA-HIPK3 expression were positively correlated with levels of VEGF, IL-1β, TNF-α and IL-6 in the DR group (P<0.05). Multivariate Logistic regression analysis showed that high levels of VEGF, circRNA-ZNF532 and circRNA-HIPK3 were risk factors for developing DR in diabetic patients (P<0.05). The areas under the curve of circRNA-ZNF532, circRNA-HIPK3 and VEGF in the diagnosis of DR in diabetic patients were 0.736, 0.740 and 0.864. Combined diagnosis was higher than that of circRNA-ZNF532, circRNA-HIPK3 and VEGF alone (P<0.05). Conclusion The up-regulated expression levels of circRNA-ZNF532 and circRNA-HIPK3 in serum of diabetic patients are related to the occurrence of DR, and both circRNA-ZNF532 and circRNA-HIPK3 can be used as potential indicators for the auxiliary diagnosis of DR.

Key words: diabetic retinopathy, RNA, circular, activating transcription factors, tristetraprolin, homeodomain proteins, inflammation, vascular endothelial growth factors, circrNa-homologous domain interaction protein kinase-3

CLC Number:

R774.13

Figures/Tables 6

References 18

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组别	n	年龄/岁		男性		BMI/（kg/m²）		吸烟史		饮酒史		糖尿病病程/年	高血压	高脂血症		DR		糖尿病周围神经病变		冠心病
对照组	65	58.76±9.62		39（60.0）		22.90±1.53		31（47.69）		26（40.0）		-	-	-		-		-		-
DM组	110	58.51±9.27		60（54.5）		22.91±1.62		63（57.27）		54（49.1）		4.91±1.32	50（45.5）	53（48.2）		21（19.1）		17（15.5）		23（20.9）
DR组	109	60.54±8.78		62（56.9）		23.05±1.79		62（56.88）		51（46.8）		7.19±2.21	71（65.1）	50（45.9）		26（23.9）		18（16.5）		21（19.3）
F、χ²或t		1.518		0.498		0.236		1.787		1.493		9.270^＊＊	8.579^＊＊	0.117		0.737		0.046		0.092
组别	脑卒中		降糖治疗				TG/ （mmol/L）		TC/ （mmol/L）		Cr/ （μmol/L）		FPG/（mmol/L）		FINS/（mmol/L）		HOMA-IR		HbA1c/%
组别	脑卒中		口服降糖药		联合胰岛素		TG/ （mmol/L）		TC/ （mmol/L）		Cr/ （μmol/L）		FPG/（mmol/L）		FINS/（mmol/L）		HOMA-IR		HbA1c/%
对照组	-		-		-		1.46±0.16		4.96±0.60		62.72±5.72		4.39±0.79		4.13±1.06		1.27±0.32		5.22±0.70
DM组	15（13.6）		65（59.1）		45（40.9）		1.89±0.25^a		5.55±0.46^a		87.81±11.05^a		7.48±1.04^a		10.11±2.05^a		3.24±0.41^a		7.69±1.09^a
DR组	17（15.6）		60（55.1）		49（44.9）		1.89±0.27^a		5.65±0.39^a		90.73±9.24^a		8.97±1.32^ab		12.38±2.41^ab		4.88±0.57^ab		9.05±0.96^ab
F、χ²或t	0.169		0.366				87.260^＊＊		47.176^＊＊		204.144^＊＊		351.408^＊＊		348.849^＊＊		1241.548^＊＊		320.678^＊＊

组别	n	年龄/岁		男性		BMI/（kg/m²）		吸烟史		饮酒史		糖尿病病程/年	高血压	高脂血症		DR		糖尿病周围神经病变		冠心病
对照组	65	58.76±9.62		39（60.0）		22.90±1.53		31（47.69）		26（40.0）		-	-	-		-		-		-
DM组	110	58.51±9.27		60（54.5）		22.91±1.62		63（57.27）		54（49.1）		4.91±1.32	50（45.5）	53（48.2）		21（19.1）		17（15.5）		23（20.9）
DR组	109	60.54±8.78		62（56.9）		23.05±1.79		62（56.88）		51（46.8）		7.19±2.21	71（65.1）	50（45.9）		26（23.9）		18（16.5）		21（19.3）
F、χ²或t		1.518		0.498		0.236		1.787		1.493		9.270^＊＊	8.579^＊＊	0.117		0.737		0.046		0.092
组别	脑卒中		降糖治疗				TG/ （mmol/L）		TC/ （mmol/L）		Cr/ （μmol/L）		FPG/（mmol/L）		FINS/（mmol/L）		HOMA-IR		HbA1c/%
组别	脑卒中		口服降糖药		联合胰岛素		TG/ （mmol/L）		TC/ （mmol/L）		Cr/ （μmol/L）		FPG/（mmol/L）		FINS/（mmol/L）		HOMA-IR		HbA1c/%
对照组	-		-		-		1.46±0.16		4.96±0.60		62.72±5.72		4.39±0.79		4.13±1.06		1.27±0.32		5.22±0.70
DM组	15（13.6）		65（59.1）		45（40.9）		1.89±0.25^a		5.55±0.46^a		87.81±11.05^a		7.48±1.04^a		10.11±2.05^a		3.24±0.41^a		7.69±1.09^a
DR组	17（15.6）		60（55.1）		49（44.9）		1.89±0.27^a		5.65±0.39^a		90.73±9.24^a		8.97±1.32^ab		12.38±2.41^ab		4.88±0.57^ab		9.05±0.96^ab
F、χ²或t	0.169		0.366				87.260^＊＊		47.176^＊＊		204.144^＊＊		351.408^＊＊		348.849^＊＊		1241.548^＊＊		320.678^＊＊

组别	n	circRNA-ZNF532	circRNA-HIPK3	VEGF/（ng/L）	IL-1β/（ng/L）	TNF-α/（ng/L）	IL-6/（ng/L）
对照组	65	1.60±0.31	1.15±0.29	48.63±13.36	62.20±12.17	3.77±1.42	49.96±9.80
DM组	110	1.65±0.34	1.21±0.24	51.83±11.79	65.54±13.83	9.10±1.97^a	60.79±16.01^a
DR组	109	5.64±1.90^ab	4.26±1.24^ab	104.90±26.06^ab	86.67±20.66^ab	13.78±2.18^ab	96.62±25.29^ab
F		371.272^＊＊	502.703^＊＊	278.583^＊＊	62.834^＊＊	546.075^＊＊	151.834^＊＊

组别	n	circRNA-ZNF532	circRNA-HIPK3	VEGF/（ng/L）	IL-1β/（ng/L）	TNF-α/（ng/L）	IL-6/（ng/L）
对照组	65	1.60±0.31	1.15±0.29	48.63±13.36	62.20±12.17	3.77±1.42	49.96±9.80
DM组	110	1.65±0.34	1.21±0.24	51.83±11.79	65.54±13.83	9.10±1.97^a	60.79±16.01^a
DR组	109	5.64±1.90^ab	4.26±1.24^ab	104.90±26.06^ab	86.67±20.66^ab	13.78±2.18^ab	96.62±25.29^ab
F		371.272^＊＊	502.703^＊＊	278.583^＊＊	62.834^＊＊	546.075^＊＊	151.834^＊＊

变量	β	SE	Wald χ²	P	OR（95%CI）
糖尿病病程	0.802	0.263	9.299	<0.001	2.230（1.332~3.734）
高血压	0.502	0.206	5.938	0.010	1.652（1.103~2.474）
HbA1c	0.904	0.277	10.651	<0.001	2.469（1.435~4.250）
circRNA- ZNF532	0.576	0.263	4.797	0.013	1.779（1.062~2.979）
circRNA- HIPK3	0.679	0.251	7.318	<0.001	1.972（1.206~3.225）
VEGF	0.602	0.279	4.656	0.019	1.826（1.057~3.155）
IL-1β	0.346	0.162	4.562	0.023	1.413（1.029~1.942）
FPG	0.264	0.251	1.106	0.365	1.302（0.796~2.130）
TNF-α	0.302	0.268	1.270	0.465	1.353（0.800~2.287）
IL-6	0.291	0.287	1.028	0.598	1.338（0.762~2.348）