ArticleBMC medical genetics2010
The CTLA4 variants may interact with the IL23R- and NOD2-conferred risk in development of Crohn's disease.
Article in BMC medical genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 18 citations in OpenAlex.
- Cytotoxic T lymphocyte-associated protein 4 gene polymorphisms are associated with ANCA-associated vasculitis in the Guangxi population of China.Frontiers in immunology · 2025Article
- Precision Cardio-Oncology: a Systems-Based Perspective on Cardiotoxicity of Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors.Journal of cardiovascular translational research · 2020Review
- Phenomic Impact of Genetically-Determined Euthyroid Function and Molecular Differences between Thyroid Disorders.Journal of clinical medicine · 2018Article
- Role of ATG16L, NOD2 and IL23R in Crohn's disease pathogenesis.World journal of gastroenterology · 2012Review
- Interaction between CTLA4 gene and IBD5 locus in Hungarian Crohn's disease patients.International journal of colorectal disease · 2011Article
- Inflammatory bowel disease associated arthropathy.Current reviews in musculoskeletal medicine · 2011Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe CTLA4 (cytotoxic T-lymphocyte antigen 4) gene is associated with several immunopathologic diseases and because of its important immuno-regulatory role it may be considered also a plausible candidate for a genetic association with inflammatory bowel diseases. Previously published studies found no association of CTLA4 with Crohn's disease itself, but some indicated an association with its subphenotypes. The aim of this study was to assess the association in the Czech population, using a set of markers shown to associate with other diseases.
methodsSix polymorphisms within the CTLA4 region were investigated in 333 patients with Crohn's disease and 482 unrelated healthy controls, all Caucasians of Czech origin. The genotypes of the SNPs were determined using the TaqMan SNP genotyping assays. Haplotypes were reconstructed using an expectation-maximization algorithm, and their association with the condition was assessed using log-linear modeling. Then, potential interactions were tested between the CTLA4 variants and other genetic factors known to confer the disease susceptibility.
resultsNo crude associations with Crohn's disease were found for the tested CTLA4 variants under the log-additive or dominant models. However, when stratified for the genetic risk conferred by the variants in the NOD2 (the p.Leu1007fsX1008, rs5743293) or the IL23R (p.R381Q, rs11209026), a significant negative association emerged for the minor alleles of CTLA4 CT60 (rs3087243), JO31 (rs11571302), JO27-1 (rs11571297) polymorphisms. This negative association with CTLA4 was apparent only in the strata defined by presence minor alleles at the NOD2 rs5743293 (here the CTLA4 CT60 A coffered an OR = 0.43, 95%CI 0.19 - 0.95 for the presence of CT60 A), or IL23R rs11209026 (here the OR for presence of CT60 A was 0.23, 95%CI 0.07 - 0.71). We observed this effect also for the haplotype consisting of minor alleles of the three tightly linked CTLA4 markers. Furthermore, this haplotype was associated with the younger age at diagnosis (OR 1.52, 95%CI 1.09 - 2.11, p = 0.014).
conclusionsA protective effect of a CTLA4 haplotype was unmasked after stratification for the risk variants in the NOD2 and IL23R genes, and may point towards the biological relevance of the molecule in the pathogenesis of the disease.
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