Cargando…
Investigation of the association between the genetic polymorphisms of the co-stimulatory system and systemic lupus erythematosus
Human leukocyte antigen genes have been shown to have the strongest association with autoimmune disease (AD). However, non-HLA genes would be risk factors of AD. Many genes encoding proteins that are related to T- and B-cell function have been identified as susceptibility genes of systemic lupus ery...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9521740/ https://www.ncbi.nlm.nih.gov/pubmed/36189300 http://dx.doi.org/10.3389/fimmu.2022.946456 |
_version_ | 1784799907668819968 |
---|---|
author | Chen, Ding-Ping Lin, Wei-Tzu Yu, Kuang-Hui |
author_facet | Chen, Ding-Ping Lin, Wei-Tzu Yu, Kuang-Hui |
author_sort | Chen, Ding-Ping |
collection | PubMed |
description | Human leukocyte antigen genes have been shown to have the strongest association with autoimmune disease (AD). However, non-HLA genes would be risk factors of AD. Many genes encoding proteins that are related to T- and B-cell function have been identified as susceptibility genes of systemic lupus erythematosus (SLE). In this study, we explored the correlation between SLE and the genetic polymorphisms of co-stimulatory/co-inhibitory molecules, including CTLA4, CD28, ICOS, PDCD1, and TNFSF4. We found that there were nine single-nucleotide polymorphisms (SNPs) associated with SLE, namely, rs11571315 (TT vs. CT vs. CC: p < 0.001; TT vs. CT: p = 0.001; p = 0.005; TT vs. CT +CC: p < 0.001; TT+CT vs. CC: p = 0.032), rs733618 (CC vs. CT vs. TT: p = 0.002; CC vs. CT: p = 0.001; CC vs. TT: p = 0.018; CC vs. CT + TT: p = 0.001), rs4553808 (AA vs. AG: p < 0.001), rs62182595 (GG vs. AG vs. AA: p < 0.001; GG vs. AG: p < 0.001; GG vs. AG+AA: p < 0.001), rs16840252 (CC vs. CT vs. TT: p < 0.001; CC vs. CT: p < 0.001; CC vs. CT + TT: p < 0.001), rs5742909 (CC vs. CT: p = 0.027; CC vs. CT + TT: p = 0.044), rs11571319 (GG vs. AG vs. AA: p < 0.001, GG vs. AG: p < 0.001; GG vs. AG+AA: p < 0.001), rs36084323 (CC vs. CT vs. TT: p = 0.013, CC vs. TT: p = 0.004; CC vs. CT + TT: p = 0.015; CC +CT vs. TT: p = 0.015), and rs1234314 (CC vs. CG vs. GG: p = 0.005; CC vs. GG: p=0.004; CC+ CG vs. GG: p=0.001), but not in CD28 and ICOS by using the chi-square test. Additionally, rs62182595 and rs16840252 of CTLA and rs1234314 and rs45454293 of TNFSF4 were also associated with SLE in haplotypes. These SLE-related SNPs also had an association with several diseases. It was indicated that these SNPs may play an important role in immune regulation and pathogenic mechanisms. |
format | Online Article Text |
id | pubmed-9521740 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95217402022-09-30 Investigation of the association between the genetic polymorphisms of the co-stimulatory system and systemic lupus erythematosus Chen, Ding-Ping Lin, Wei-Tzu Yu, Kuang-Hui Front Immunol Immunology Human leukocyte antigen genes have been shown to have the strongest association with autoimmune disease (AD). However, non-HLA genes would be risk factors of AD. Many genes encoding proteins that are related to T- and B-cell function have been identified as susceptibility genes of systemic lupus erythematosus (SLE). In this study, we explored the correlation between SLE and the genetic polymorphisms of co-stimulatory/co-inhibitory molecules, including CTLA4, CD28, ICOS, PDCD1, and TNFSF4. We found that there were nine single-nucleotide polymorphisms (SNPs) associated with SLE, namely, rs11571315 (TT vs. CT vs. CC: p < 0.001; TT vs. CT: p = 0.001; p = 0.005; TT vs. CT +CC: p < 0.001; TT+CT vs. CC: p = 0.032), rs733618 (CC vs. CT vs. TT: p = 0.002; CC vs. CT: p = 0.001; CC vs. TT: p = 0.018; CC vs. CT + TT: p = 0.001), rs4553808 (AA vs. AG: p < 0.001), rs62182595 (GG vs. AG vs. AA: p < 0.001; GG vs. AG: p < 0.001; GG vs. AG+AA: p < 0.001), rs16840252 (CC vs. CT vs. TT: p < 0.001; CC vs. CT: p < 0.001; CC vs. CT + TT: p < 0.001), rs5742909 (CC vs. CT: p = 0.027; CC vs. CT + TT: p = 0.044), rs11571319 (GG vs. AG vs. AA: p < 0.001, GG vs. AG: p < 0.001; GG vs. AG+AA: p < 0.001), rs36084323 (CC vs. CT vs. TT: p = 0.013, CC vs. TT: p = 0.004; CC vs. CT + TT: p = 0.015; CC +CT vs. TT: p = 0.015), and rs1234314 (CC vs. CG vs. GG: p = 0.005; CC vs. GG: p=0.004; CC+ CG vs. GG: p=0.001), but not in CD28 and ICOS by using the chi-square test. Additionally, rs62182595 and rs16840252 of CTLA and rs1234314 and rs45454293 of TNFSF4 were also associated with SLE in haplotypes. These SLE-related SNPs also had an association with several diseases. It was indicated that these SNPs may play an important role in immune regulation and pathogenic mechanisms. Frontiers Media S.A. 2022-09-06 /pmc/articles/PMC9521740/ /pubmed/36189300 http://dx.doi.org/10.3389/fimmu.2022.946456 Text en Copyright © 2022 Chen, Lin and Yu 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 Chen, Ding-Ping Lin, Wei-Tzu Yu, Kuang-Hui Investigation of the association between the genetic polymorphisms of the co-stimulatory system and systemic lupus erythematosus |
title | Investigation of the association between the genetic polymorphisms of the co-stimulatory system and systemic lupus erythematosus |
title_full | Investigation of the association between the genetic polymorphisms of the co-stimulatory system and systemic lupus erythematosus |
title_fullStr | Investigation of the association between the genetic polymorphisms of the co-stimulatory system and systemic lupus erythematosus |
title_full_unstemmed | Investigation of the association between the genetic polymorphisms of the co-stimulatory system and systemic lupus erythematosus |
title_short | Investigation of the association between the genetic polymorphisms of the co-stimulatory system and systemic lupus erythematosus |
title_sort | investigation of the association between the genetic polymorphisms of the co-stimulatory system and systemic lupus erythematosus |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9521740/ https://www.ncbi.nlm.nih.gov/pubmed/36189300 http://dx.doi.org/10.3389/fimmu.2022.946456 |
work_keys_str_mv | AT chendingping investigationoftheassociationbetweenthegeneticpolymorphismsofthecostimulatorysystemandsystemiclupuserythematosus AT linweitzu investigationoftheassociationbetweenthegeneticpolymorphismsofthecostimulatorysystemandsystemiclupuserythematosus AT yukuanghui investigationoftheassociationbetweenthegeneticpolymorphismsofthecostimulatorysystemandsystemiclupuserythematosus |