Abstract: SA-PO651
Genome-Wide Methylation in Patients With Primary IgA Nephropathy
Session Information
- Glomerular Diseases: IgA and Complement-Mediated GN
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1302 Glomerular Diseases: Immunology and Inflammation
Authors
- Wang, Qiuxia, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China
- Wang, Wei, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China
Background
Methylation gene chip was used to study the pathogenesis of DNA methylation in IgAN.
Methods
NimbleGen 3x720K methylation gene chip was used to screen differentially methylation genes (DMGs) in patients with IgA nephropathy and healthy subjects combining with functional enrichment analysis. The mRNA expression of DMGs in peripheral blood lymphocytes was screened by RT-qPCR; the methylation level of DMGs was verified by pyrophosphate sequencing; the relationship between the methylation level of DMGs and mRNA expression level and clinical characteristics were analyzed.
Results
1. 2062 differentially methylation sites and 1839 differentially methylation genes were detected by methylation gene chip. 2. Four differentially methylation genes CLEC10A, ACCS, CFHR1 and TNFRSF17 were screened by functional enrichment analysis. 3. RT-qPCR showed that, in peripheral blood lymphocytes of IgAN group, the mRNA expression level of TNFRSF17 was higher than that of control group (P=0.03). 4. Combined with the clinical data, in peripheral blood lymphocytes of patients with IgAN, the mRNA expression level of CLEC10A was negatively correlated with hemoglobin (P=0.02, r=-0.33); the mRNA expression level of TNFRSF17 was negatively correlated with high density lipoprotein (P=0.04, r=-0.33); the mRNA expression level of CFHR1 was negatively correlated with eGFR level (P=0.03, r=-0.31) and positively correlated with the level of serum creatinine (P=0.06, r=0.27). 5. According to the analysis of pathological data, the mRNA expression level of CLEC10A in E1 group was higher than that in E0 group, and that in S1 group was higher than that in S0 group (P < 0.05). Compared with M0, E0 and C0, the mRNA expression level of TNFRSF17 increased in M1, E1 and C1~2 groups, but the difference was not statistically significant. 6. In IgAN group, the methylation level of TNFRSF17 CpG1 site was increased(P=0.02), and it was positively correlated with the expression level of TNFRSF17 mRNA (P<0.05, r=0.39).
Conclusion
1. Aberrant DNA methylation of TNFRSF17 may be involved in the pathogenesis of IgAN.
2. CFHR1 and CLEC10A may be related to the disease progression of IgAN.