CD28 and CTLA4 polymorphisms associated with ankylosing spondylitis: a study in the context of HLA-B27
Abstract Background The human leukocyte antigen (HLA)-B27 gene is highly associated with ankylosing spondylitis (AS). However, not everyone who carries the HLA-B27 antigen develops AS, indicating that factors beyond the HLA-B27 gene contribute to the disease’s onset. AS is an autoimmune disease in w...
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2025-05-01
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| Series: | BMC Immunology |
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| Online Access: | https://doi.org/10.1186/s12865-025-00720-9 |
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| author | Kuang-Hui Yu Gem Huai-Chueh Wu Chia-Ju Yang Wei-Tzu Lin Fang-Ping Hsu Ding-Ping Chen |
| author_facet | Kuang-Hui Yu Gem Huai-Chueh Wu Chia-Ju Yang Wei-Tzu Lin Fang-Ping Hsu Ding-Ping Chen |
| author_sort | Kuang-Hui Yu |
| collection | DOAJ |
| description | Abstract Background The human leukocyte antigen (HLA)-B27 gene is highly associated with ankylosing spondylitis (AS). However, not everyone who carries the HLA-B27 antigen develops AS, indicating that factors beyond the HLA-B27 gene contribute to the disease’s onset. AS is an autoimmune disease in which co-stimulatory systems have been widely explored. Therefore, we aimed to analyze the association between single-nucleotide polymorphisms (SNPs) in co-stimulatory/inhibitory molecules and AS to identify other key factors involved in developing the disease. Results This study recruited 32 patients with AS and 32 controls. DNA was extracted from whole blood, and PCR amplification was performed to target the promoter regions of the CTLA4, CD28, and PDCD1 genes. Chi-square and Fisher’s exact tests were used under various genetic models to assess differences in genotype and allele distribution between cases and controls. The results showed that rs201801072 of the CD28 gene (TT + CT vs. CC, p = 0.001) and rs11571319 of the CTLA4 gene were associated with AS (GG vs. AG + AA, p = 0.001). Logistic regression analysis showed that rs201801072 (CD28) and rs11571319 (CTLA4) were independently associated with AS. A significant positive interaction was observed between these SNPs and HLA-B27 positivity, further increasing the risk of AS (T-allele: OR = 6.15; G-allele: OR = 13.30, both p < 0.001). HLA-B27 carriers exhibited an extremely high risk of AS (OR = 65.0, p = 1.19E-06). Conclusions The elevated frequencies of specific alleles in AS patients compared to controls highlight the potential involvement of these SNPs as key factors in the pathogenesis of AS, offering new insights into the genetic mechanisms underlying the disease. |
| format | Article |
| id | doaj-art-cf93d5c85d814e14a2acccb08a025840 |
| institution | DOAJ |
| issn | 1471-2172 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Immunology |
| spelling | doaj-art-cf93d5c85d814e14a2acccb08a0258402025-08-20T03:08:24ZengBMCBMC Immunology1471-21722025-05-012611710.1186/s12865-025-00720-9CD28 and CTLA4 polymorphisms associated with ankylosing spondylitis: a study in the context of HLA-B27Kuang-Hui Yu0Gem Huai-Chueh Wu1Chia-Ju Yang2Wei-Tzu Lin3Fang-Ping Hsu4Ding-Ping Chen5Division of Rheumatology, Allergy, and Immunology, Chang Gung University and Linkou Chang Gung Memorial HospitalDivision of Hematology, Linkou Chang Gung Memorial HospitalDepartment of Laboratory Medicine, Linkou Chang Gung Memorial HospitalDepartment of Laboratory Medicine, Linkou Chang Gung Memorial HospitalDepartment of Laboratory Medicine, Linkou Chang Gung Memorial HospitalDepartment of Laboratory Medicine, Linkou Chang Gung Memorial HospitalAbstract Background The human leukocyte antigen (HLA)-B27 gene is highly associated with ankylosing spondylitis (AS). However, not everyone who carries the HLA-B27 antigen develops AS, indicating that factors beyond the HLA-B27 gene contribute to the disease’s onset. AS is an autoimmune disease in which co-stimulatory systems have been widely explored. Therefore, we aimed to analyze the association between single-nucleotide polymorphisms (SNPs) in co-stimulatory/inhibitory molecules and AS to identify other key factors involved in developing the disease. Results This study recruited 32 patients with AS and 32 controls. DNA was extracted from whole blood, and PCR amplification was performed to target the promoter regions of the CTLA4, CD28, and PDCD1 genes. Chi-square and Fisher’s exact tests were used under various genetic models to assess differences in genotype and allele distribution between cases and controls. The results showed that rs201801072 of the CD28 gene (TT + CT vs. CC, p = 0.001) and rs11571319 of the CTLA4 gene were associated with AS (GG vs. AG + AA, p = 0.001). Logistic regression analysis showed that rs201801072 (CD28) and rs11571319 (CTLA4) were independently associated with AS. A significant positive interaction was observed between these SNPs and HLA-B27 positivity, further increasing the risk of AS (T-allele: OR = 6.15; G-allele: OR = 13.30, both p < 0.001). HLA-B27 carriers exhibited an extremely high risk of AS (OR = 65.0, p = 1.19E-06). Conclusions The elevated frequencies of specific alleles in AS patients compared to controls highlight the potential involvement of these SNPs as key factors in the pathogenesis of AS, offering new insights into the genetic mechanisms underlying the disease.https://doi.org/10.1186/s12865-025-00720-9Ankylosing spondylitisHLA-B27CD28CTLA4Single nucleotide polymorphism (SNP) |
| spellingShingle | Kuang-Hui Yu Gem Huai-Chueh Wu Chia-Ju Yang Wei-Tzu Lin Fang-Ping Hsu Ding-Ping Chen CD28 and CTLA4 polymorphisms associated with ankylosing spondylitis: a study in the context of HLA-B27 BMC Immunology Ankylosing spondylitis HLA-B27 CD28 CTLA4 Single nucleotide polymorphism (SNP) |
| title | CD28 and CTLA4 polymorphisms associated with ankylosing spondylitis: a study in the context of HLA-B27 |
| title_full | CD28 and CTLA4 polymorphisms associated with ankylosing spondylitis: a study in the context of HLA-B27 |
| title_fullStr | CD28 and CTLA4 polymorphisms associated with ankylosing spondylitis: a study in the context of HLA-B27 |
| title_full_unstemmed | CD28 and CTLA4 polymorphisms associated with ankylosing spondylitis: a study in the context of HLA-B27 |
| title_short | CD28 and CTLA4 polymorphisms associated with ankylosing spondylitis: a study in the context of HLA-B27 |
| title_sort | cd28 and ctla4 polymorphisms associated with ankylosing spondylitis a study in the context of hla b27 |
| topic | Ankylosing spondylitis HLA-B27 CD28 CTLA4 Single nucleotide polymorphism (SNP) |
| url | https://doi.org/10.1186/s12865-025-00720-9 |
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