Analysis Of The Relationship Between The Expression Level Of UP? And Agtr2 Genes DNA Methylation And The Clinical Characteristics Of Children With Vesicoureteral Reflux

Objective The purpose of this study was to analyze the possible difference of DNA methylation level of Uroplakin ?(UPIII)and Angiotensin ? type 2Receptor(Agtr2)genes between children with vesicoureteral reflux(VUR)and healthy children,and to provide new clinical data and ideas for the study of epigenetics of VUR.Methods In this study,14 VUR cases were collected from the Department of Pediatrics of Gansu Provincial people's Hospital from December 2017 to June2019.The average age was 3.70(2.05-8.90),and the sex ratio was 7/7.In the same period,11 healthy children who underwent physical examination in the child health clinic were collected as the control group,with an average age of 4.10(2.00-7.30)years,and the male-to-female ratio was 5/6.The DNA methylation level of UPIII and Agtr2 gene in serum of all samples was detected by bisulfite sequencing,and serum creatinine(SCr),uric acid(UA),blood urea nitrogen(BUN)and 24-hour urinary protein were detected by biochemical analyzer.Results 1.There was no difference in sex and age between the VUR group and the control group(P>0.05).The systolic blood pressure and diastolic blood pressure in the VUR group were significantly higher than those in the healthy control group(P<0.05).2.The levels of BUN and UA in VUR group were significantly higher than those in healthy control group(P<0.05).There was no difference in SCr betweenVUR group and control group(P>0.05).3.There was no correlation between the degree of reflux and 24-hour urinary protein and estimated glomerular filtration rate evaluated glomerular filtration(eGFR)in VUR group(P>0.05).4.There was no correlation between the age and the degree of reflux,24-hour urinary protein and eGFR in VUR group(P>0.05).5.The average methylation rate of the CpG1561 locus of Agtr2 was 96.7% in the case group and 95.8% in the control group.There was no significant difference between the case group and the control group(P>0.05).6.Methylation rate of CpG1-6,8,10-12 sites in the promoter region of UPIII gene in VUR group.It was higher than that in the control group,and the difference was statistically significant(P?0.05).7.The methylation rates of CpG3,5-8 and 10-12 sites in the promoter region of UPIII gene were significantly different in children with VUR with different degrees of reflux(P<0.05).Conclusion 1.Children with VUR are more likely to have elevated blood pressure than healthy children,suggesting the importance of strengthening the management of extrarenal complications of VUR in the early stage.2.CpG1-6,8,10-12 loci in the promoter region of UPIII gene in VUR group.The methylation rate of UPIII gene was significantly higher than that of the control group,and there was a difference in the expression of DNA methylation in the promoter region of UPIII gene in children with VUR with different degrees of reflux.Our study provides new clinical data for the study of the epigenetic molecular mechanism of VUR and the involvement of urinary tract proteins in the function of urothelial epithelium in children with VUR in the future.