Min Feng, Fanxing Meng, Yanlin Wang, Yuhan Jia, Guozhen Ji, Yue Jin, Chong Gao, Jing Luo
{"title":"评估Foxp3和CTLA-4基因多态性在原发性Sjögren综合征免疫平衡和疾病易感性中的潜在影响","authors":"Min Feng, Fanxing Meng, Yanlin Wang, Yuhan Jia, Guozhen Ji, Yue Jin, Chong Gao, Jing Luo","doi":"10.1097/FPC.0000000000000567","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Regulatory T (Treg) cell depletion-associated immune tolerance deficiency have been shown to play a key role in the pathogenesis of primary Sjögren's syndrome (pSS). Treg cells mainly express the transcriptional regulator Foxp3 and are characterized by constitutively high expression of inhibitory coreceptor CTLA-4 . Herein, the aim of this study was to investigate the potential association of single nucleotide polymorphisms (SNPs) in Foxp3 and CTLA-4 genes with the susceptibility to pSS.</p><p><strong>Method: </strong>Ninety-nine pSS patients and 93 healthy controls were recruited into the retrospective study. Nuclear DNA was extracted from peripheral blood leukocytes, and SNP alleles were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.</p><p><strong>Results: </strong>For the Foxp3 gene, the T allele, the TT and GT genotype in rs3761548G/T, the A allele and AA genotype in rs3761549G/A, as well as the C allele and the TC genotype in rs2280883T/C, were preponderant in pSS. Polymorphisms of rs3761548G/T and rs3761549G/A were found to be associated with anemia or leukopenia, while rs2232365T/C was associated with neutropenia, and rs2280883T/C was demonstrated to have a correlation with anti-SSA(+). For the CTLA-4 gene, the C allele and the CC genotype in rs733618T/C were significantly more prevalent in pSS. rs733618T/C polymorphisms varied significantly in anti-SSA(+), anti-SSB(+) and leukopenia, and rs16840252T/C was associated with ANA(+). Patients with at least six risk alleles had higher Th17 cells and decreased Treg cell counts, accompanied by elevated Th1/Treg, Th2/Treg, and Th17/Treg ratios. And the phenomenon was also observed in patients with four or more variant genotypes.</p><p><strong>Conclusion: </strong>Polymorphisms in Foxp3 and CTLA-4 genes were associated with the susceptibility to pSS. The greater number of mutant sites and variant genotypes an individual possessed, the more susceptible they became to immune dysregulation.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"159-169"},"PeriodicalIF":1.7000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Assessment of the potential impact of polymorphisms in the Foxp3 and CTLA-4 genes in immune balance and disease susceptibility of primary Sjögren's syndrome.\",\"authors\":\"Min Feng, Fanxing Meng, Yanlin Wang, Yuhan Jia, Guozhen Ji, Yue Jin, Chong Gao, Jing Luo\",\"doi\":\"10.1097/FPC.0000000000000567\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Regulatory T (Treg) cell depletion-associated immune tolerance deficiency have been shown to play a key role in the pathogenesis of primary Sjögren's syndrome (pSS). Treg cells mainly express the transcriptional regulator Foxp3 and are characterized by constitutively high expression of inhibitory coreceptor CTLA-4 . Herein, the aim of this study was to investigate the potential association of single nucleotide polymorphisms (SNPs) in Foxp3 and CTLA-4 genes with the susceptibility to pSS.</p><p><strong>Method: </strong>Ninety-nine pSS patients and 93 healthy controls were recruited into the retrospective study. Nuclear DNA was extracted from peripheral blood leukocytes, and SNP alleles were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.</p><p><strong>Results: </strong>For the Foxp3 gene, the T allele, the TT and GT genotype in rs3761548G/T, the A allele and AA genotype in rs3761549G/A, as well as the C allele and the TC genotype in rs2280883T/C, were preponderant in pSS. Polymorphisms of rs3761548G/T and rs3761549G/A were found to be associated with anemia or leukopenia, while rs2232365T/C was associated with neutropenia, and rs2280883T/C was demonstrated to have a correlation with anti-SSA(+). For the CTLA-4 gene, the C allele and the CC genotype in rs733618T/C were significantly more prevalent in pSS. rs733618T/C polymorphisms varied significantly in anti-SSA(+), anti-SSB(+) and leukopenia, and rs16840252T/C was associated with ANA(+). Patients with at least six risk alleles had higher Th17 cells and decreased Treg cell counts, accompanied by elevated Th1/Treg, Th2/Treg, and Th17/Treg ratios. And the phenomenon was also observed in patients with four or more variant genotypes.</p><p><strong>Conclusion: </strong>Polymorphisms in Foxp3 and CTLA-4 genes were associated with the susceptibility to pSS. The greater number of mutant sites and variant genotypes an individual possessed, the more susceptible they became to immune dysregulation.</p>\",\"PeriodicalId\":19763,\"journal\":{\"name\":\"Pharmacogenetics and genomics\",\"volume\":\" \",\"pages\":\"159-169\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacogenetics and genomics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/FPC.0000000000000567\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/4/17 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacogenetics and genomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/FPC.0000000000000567","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/17 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Assessment of the potential impact of polymorphisms in the Foxp3 and CTLA-4 genes in immune balance and disease susceptibility of primary Sjögren's syndrome.
Background: Regulatory T (Treg) cell depletion-associated immune tolerance deficiency have been shown to play a key role in the pathogenesis of primary Sjögren's syndrome (pSS). Treg cells mainly express the transcriptional regulator Foxp3 and are characterized by constitutively high expression of inhibitory coreceptor CTLA-4 . Herein, the aim of this study was to investigate the potential association of single nucleotide polymorphisms (SNPs) in Foxp3 and CTLA-4 genes with the susceptibility to pSS.
Method: Ninety-nine pSS patients and 93 healthy controls were recruited into the retrospective study. Nuclear DNA was extracted from peripheral blood leukocytes, and SNP alleles were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
Results: For the Foxp3 gene, the T allele, the TT and GT genotype in rs3761548G/T, the A allele and AA genotype in rs3761549G/A, as well as the C allele and the TC genotype in rs2280883T/C, were preponderant in pSS. Polymorphisms of rs3761548G/T and rs3761549G/A were found to be associated with anemia or leukopenia, while rs2232365T/C was associated with neutropenia, and rs2280883T/C was demonstrated to have a correlation with anti-SSA(+). For the CTLA-4 gene, the C allele and the CC genotype in rs733618T/C were significantly more prevalent in pSS. rs733618T/C polymorphisms varied significantly in anti-SSA(+), anti-SSB(+) and leukopenia, and rs16840252T/C was associated with ANA(+). Patients with at least six risk alleles had higher Th17 cells and decreased Treg cell counts, accompanied by elevated Th1/Treg, Th2/Treg, and Th17/Treg ratios. And the phenomenon was also observed in patients with four or more variant genotypes.
Conclusion: Polymorphisms in Foxp3 and CTLA-4 genes were associated with the susceptibility to pSS. The greater number of mutant sites and variant genotypes an individual possessed, the more susceptible they became to immune dysregulation.
期刊介绍：
Pharmacogenetics and Genomics is devoted to the rapid publication of research papers, brief review articles and short communications on genetic determinants in response to drugs and other chemicals in humans and animals. The Journal brings together papers from the entire spectrum of biomedical research and science, including biochemistry, bioinformatics, clinical pharmacology, clinical pharmacy, epidemiology, genetics, genomics, molecular biology, pharmacology, pharmaceutical sciences, and toxicology. Under a single cover, the Journal provides a forum for all aspects of the genetics and genomics of host response to exogenous chemicals: from the gene to the clinic.
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