Abstract: TH-PO531
Effects of Multilocus Interaction on IgA Nephropathy in the Chinese Han Population
Session Information
- Glomerular Diseases: Omics, Biomarkers, and Tools
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Shi, Dianchun, Guangdong Provincial People’s Hospital, Guangzhou, China
- Yuanyuan, Wu, Guangdong Provincial People’s Hospital, Guangzhou, China
- Yu, Xueqing, Guangdong Provincial People’s Hospital, Guangzhou, China
- Ming, Li, Guangdong Provincial People’s Hospital, Guangzhou, China
Background
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Previous genome-wide association studies (GWAS) have identified multiple susceptibility genes for IgAN, including TNFSF13, ITGAX-ITGAM, FCRL3, ST6GAL1 and CARD9. Gene-gene interaction might have more influence on the susceptibility of IgAN and advance our understanding of the genetic pathogenesis of IgAN. This study aims to investigate the correlation between the gene-gene interaction and IgAN susceptibility.
Methods
A total of 63 single-nucleotide polymorphisms (SNPs) were selected for genotyping by using MassARRAY platform in 1,000 IgAN cases and 1,000 healthy controls.Data quality control and filtering were conducted using PLINK 1.90, and the frequency distribution of genotypes and alleles were calculated. Multifactor dimensionality reduction (GMDR) method was used to analyze the multi-step gene-gene interactions.
Results
The GMDR analysis revealed that the interaction of TNFSF13 (rs4968210), FCRL3 (rs11264793), and ST6GAL1 (rs2284750, rs7634389) was significantly associated with the risk of IgAN (P=0.01, OR=2.88). In addition, the genotype–phenotype association analysis showed that the interaction of TNFSF13 (rs3803800), FCRL3 (rs11264793, rs7528684), ITGAX (rs11150619) and ST6GAL1 (rs6784233, rs7634389) was associated with eGFR in IgAN patients (P=0.01, OR=14.03). The TNFSF13 (rs3803800), FCRL3 (rs11264793, rs7528684), ITGAX (rs11150614), and ST6GAL1 (rs7634389) had combined effects on the low density lipoprotein in IgAN patients (P=0.01, OR=4.81). Furthermore, the interaction of TNFSF13 (rs3803800), FCRL3 (rs11264793, rs7528684), ITGAX (rs7190997) and ST6GAL1 (rs6784233, rs7634389) was also associated with hematuria in IgAN patients (P=0.001, OR=29.66).
Conclusion
The study suggested that the interaction of ITGAX-ITGAM, TNFSF13, FCRL3 and ST6GAL1 genes might have some influence on the susceptibility to IgAN. Additionally, it may also correlate with the lipid levels, hematuria, and the progression of renal function in patients.