Related Experiment Video
Updated: Nov 13, 2025
Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
A Functional Variant rs3093023 in CCR6 Is Associated With IgA Nephropathy by Regulating Th17 Cells in a North Han
Yue-Miao Zhang1,2,3, Xing-Zi Liu1,2,3, Xu-Jie Zhou1,2,3
1Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
Insights
The C-C chemokine receptor 6 (CCR6) gene variant rs3093023 is linked to immunoglobulin A nephropathy (IgAN) susceptibility. This variant influences Th17 cell regulation, potentially impacting disease development.
Area of Science:
- Immunogenetics
- Nephrology
- Molecular Biology
Background:
- C-C chemokine receptor 6 (CCR6) is implicated in immune-related diseases.
- CCR6 variants are suggested to play a role in immunoglobulin A nephropathy (IgAN) pathogenesis.
- Identifying functional variants is crucial for understanding IgAN susceptibility.
Purpose of the Study:
- To identify functional variants within the CCR6 gene associated with IgAN susceptibility.
- To elucidate the molecular mechanisms by which CCR6 variants contribute to IgAN.
Main Methods:
- Genome-wide association study (GWAS) with imputation to analyze CCR6 common and rare variants.
- Expression quantitative trait loci (eQTL) analysis to assess variant effects on gene expression.
- Electrophoretic mobility shift assay (EMSA) to investigate protein-DNA binding.
- Analysis of CCR6 mRNA and protein levels, and correlations with immune cell populations and clinical parameters.
Main Results:
- Sixty-eight significantly associated common variants in the CCR6 regulatory region were identified.
- The variant rs3093023 demonstrated a significant association with IgAN susceptibility and an eQTL effect.
- rs3093023 alleles influenced nuclear protein binding and were associated with increased CCR6+ T cells, diastolic blood pressure, serum creatinine, and tubular atrophy/interstitial fibrosis.
Conclusions:
- The rs3093023 variant in CCR6 is prioritized as a functional variant contributing to IgAN susceptibility.
- This variant may exert its effect by regulating Th17 cell differentiation and function.
- Findings provide insights into the genetic basis of IgAN and potential therapeutic targets.
Abstract:
C-C chemokine receptor 6 (CCR6) is a susceptibility gene of various immune-related diseases, which was suggested to be shared with immunoglobulin A nephropathy (IgAN). In this study, we aimed to identify the functional variants. First, we analyzed the associations of CCR6 common and rare variants detected by multi-platform chips with IgAN susceptibility using imputation and identified 68 significantly associated common variants located in the regulatory region. Among them, rs3093023 showed both statistical significance (rs3093023-A, odds ratio [OR] = 1.15, P = 2.00 × 10-2) and the expression quantitative trait loci (eQTL) effect (P = 1.45 × 10-3). It was independently replicated (rs3093023-A, OR = 1.18, P = 5.56 × 10-3) and the association was reinforced in the meta-analysis (rs3093023-A, OR = 1.17, P = 6.14 × 10-7). Although rs3093023 was in a strong linkage disequilibrium with the reported CCR6 functional variant dinucleotide polymorphism, CCR6DNP, the alleles of rs3093023 (G>A) rather than of CCR6DNP were shown differential nuclear protein binding effect by electrophoretic mobility shift assay. The RegulomeDB and JASPAR databases predicted Pou2f1 as the potential transcription factor, which was negatively associated with CCR6 mRNA (r = -0.60, P = 3.94 × 10-9). At the mRNA level, the eQTL effect of CCR6 was validated (P = 4.39 × 10-2), and CCR6 was positively associated with the expression of CCR4 and IL-17A rather than that of CXCR3 and IFNG. At the protein level, a higher CCR6+ cell ratio was observed in a risk allele dose-dependent manner in lymphocytes (P = 3.57 × 10-2), CD3+ T cells (P = 4.54 × 10-2), and CD4+ T cells (P = 1.32 × 10-2), but not in CD8+ T cells. Clinical-pathological analysis showed that rs3093023 risk allele was significantly associated with diastolic blood pressure, serum creatinine, and high ratio of tubular atrophy/interstitial fibrosis. Overall, the rs3093023 was prioritized as the function variant in CCR6, which may contribute to IgAN susceptibility by regulating Th17 cells.
More Related Videos
07:26High-resolution Melting PCR for Complement Receptor 1 Length Polymorphism Genotyping: An Innovative Tool for Alzheimer's Disease Gene Susceptibility Assessment
Published on: July 18, 2017
05:39Detection of MicroRNA Expression in the Kidneys of Immunoglobulin A Nephropathic Mice
Published on: July 8, 2020
Related Concept Videos
01:05Single Nucleotide Polymorphisms-SNPs
01:11Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...