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The Contribution of Genetic Variation and Aberrant Methylation of Aryl Hydrocarbon Receptor Signaling Pathway Genes to Rheumatoid Arthritis

The aryl hydrocarbon receptor (AHR) signaling pathway participates in immune regulation of multiple autoimmune diseases, including rheumatoid arthritis (RA). We conducted this study to investigate the association of AHR signaling pathway genes (AHR, ARNT, AHRR) single nucleotide polymorphisms (SNPs)...

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Autores principales: Zhang, Tian-Ping, Li, Rui, Li, Hong-Miao, Xiang, Nan, Tan, Zhen, Wang, Guo-Sheng, Li, Xiao-Mei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8924038/
https://www.ncbi.nlm.nih.gov/pubmed/35309329
http://dx.doi.org/10.3389/fimmu.2022.823863
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author Zhang, Tian-Ping
Li, Rui
Li, Hong-Miao
Xiang, Nan
Tan, Zhen
Wang, Guo-Sheng
Li, Xiao-Mei
author_facet Zhang, Tian-Ping
Li, Rui
Li, Hong-Miao
Xiang, Nan
Tan, Zhen
Wang, Guo-Sheng
Li, Xiao-Mei
author_sort Zhang, Tian-Ping
collection PubMed
description The aryl hydrocarbon receptor (AHR) signaling pathway participates in immune regulation of multiple autoimmune diseases, including rheumatoid arthritis (RA). We conducted this study to investigate the association of AHR signaling pathway genes (AHR, ARNT, AHRR) single nucleotide polymorphisms (SNPs), as well as their methylation levels, with RA susceptibility. Nine SNPs (AHR gene rs2066853, rs2158041, rs2282885, ARNT gene rs10847, rs1889740, rs11204735, AHRR gene rs2292596, rs2672725, rs349583) were genotyped via improved multiple ligase detection reaction (iMLDR) in 479 RA patients and 496 healthy controls. We used the Illumina Hiseq platform to detect methylation levels of these genes in 122 RA patients and 123 healthy controls. A significant increase in rs11204735 C allele frequency was observed in RA patients when compared to controls. Further, rs11204735 polymorphism was associated with a decreased risk of RA under the dominant model. ARNT CCC haplotype frequency was significantly increased in RA patients in comparison to controls. In the AHRR gene, rs2672725 GG genotype, G allele frequencies were significantly related to an increased risk of RA and rs2292596, rs2672725 polymorphism were significantly associated with an increased risk of RA under the dominant model, recessive model, respectively. However, no significant association was identified between AHR gene polymorphism and RA susceptibility. The AHR methylation level in RA patients was significantly higher than the controls, while AHRR methylation level was abnormally reduced in RA patients. In addition, AHRR rs2672725 genotype distribution was significantly associated with the AHRR methylation level among RA patients. In summary, ARNT rs11204735, AHRR rs2292596, and rs2672725 polymorphisms were associated with RA susceptibility and altered AHR, AHRR methylation levels were related to the risk of RA.
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spelling pubmed-89240382022-03-17 The Contribution of Genetic Variation and Aberrant Methylation of Aryl Hydrocarbon Receptor Signaling Pathway Genes to Rheumatoid Arthritis Zhang, Tian-Ping Li, Rui Li, Hong-Miao Xiang, Nan Tan, Zhen Wang, Guo-Sheng Li, Xiao-Mei Front Immunol Immunology The aryl hydrocarbon receptor (AHR) signaling pathway participates in immune regulation of multiple autoimmune diseases, including rheumatoid arthritis (RA). We conducted this study to investigate the association of AHR signaling pathway genes (AHR, ARNT, AHRR) single nucleotide polymorphisms (SNPs), as well as their methylation levels, with RA susceptibility. Nine SNPs (AHR gene rs2066853, rs2158041, rs2282885, ARNT gene rs10847, rs1889740, rs11204735, AHRR gene rs2292596, rs2672725, rs349583) were genotyped via improved multiple ligase detection reaction (iMLDR) in 479 RA patients and 496 healthy controls. We used the Illumina Hiseq platform to detect methylation levels of these genes in 122 RA patients and 123 healthy controls. A significant increase in rs11204735 C allele frequency was observed in RA patients when compared to controls. Further, rs11204735 polymorphism was associated with a decreased risk of RA under the dominant model. ARNT CCC haplotype frequency was significantly increased in RA patients in comparison to controls. In the AHRR gene, rs2672725 GG genotype, G allele frequencies were significantly related to an increased risk of RA and rs2292596, rs2672725 polymorphism were significantly associated with an increased risk of RA under the dominant model, recessive model, respectively. However, no significant association was identified between AHR gene polymorphism and RA susceptibility. The AHR methylation level in RA patients was significantly higher than the controls, while AHRR methylation level was abnormally reduced in RA patients. In addition, AHRR rs2672725 genotype distribution was significantly associated with the AHRR methylation level among RA patients. In summary, ARNT rs11204735, AHRR rs2292596, and rs2672725 polymorphisms were associated with RA susceptibility and altered AHR, AHRR methylation levels were related to the risk of RA. Frontiers Media S.A. 2022-03-02 /pmc/articles/PMC8924038/ /pubmed/35309329 http://dx.doi.org/10.3389/fimmu.2022.823863 Text en Copyright © 2022 Zhang, Li, Li, Xiang, Tan, Wang and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zhang, Tian-Ping
Li, Rui
Li, Hong-Miao
Xiang, Nan
Tan, Zhen
Wang, Guo-Sheng
Li, Xiao-Mei
The Contribution of Genetic Variation and Aberrant Methylation of Aryl Hydrocarbon Receptor Signaling Pathway Genes to Rheumatoid Arthritis
title The Contribution of Genetic Variation and Aberrant Methylation of Aryl Hydrocarbon Receptor Signaling Pathway Genes to Rheumatoid Arthritis
title_full The Contribution of Genetic Variation and Aberrant Methylation of Aryl Hydrocarbon Receptor Signaling Pathway Genes to Rheumatoid Arthritis
title_fullStr The Contribution of Genetic Variation and Aberrant Methylation of Aryl Hydrocarbon Receptor Signaling Pathway Genes to Rheumatoid Arthritis
title_full_unstemmed The Contribution of Genetic Variation and Aberrant Methylation of Aryl Hydrocarbon Receptor Signaling Pathway Genes to Rheumatoid Arthritis
title_short The Contribution of Genetic Variation and Aberrant Methylation of Aryl Hydrocarbon Receptor Signaling Pathway Genes to Rheumatoid Arthritis
title_sort contribution of genetic variation and aberrant methylation of aryl hydrocarbon receptor signaling pathway genes to rheumatoid arthritis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8924038/
https://www.ncbi.nlm.nih.gov/pubmed/35309329
http://dx.doi.org/10.3389/fimmu.2022.823863
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