AUTHOR=Chen Ding-Ping , Lin Wei-Tzu , Yu Kuang-Hui 

TITLE=Investigation of the association between the genetic polymorphisms of the co-stimulatory system and systemic lupus erythematosus

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.946456

DOI=10.3389/fimmu.2022.946456

ISSN=1664-3224

ABSTRACT=The human leukocyte antigen genes have been shown that it has 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 9 single nucleotide polymorphisms (SNPs) associated with SLE, including 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; GG vs. CC: p=0.004; GG+ CG vs. CC: p=0.001), but no in CD28 and ICOS by using 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 association with several diseases. It was indicated that these SNPs may play an important role in immune regulation and pathogenic mechanisms.