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CTLA4 CT60 single-nucleotide polymorphism is associated with Slovenian inflammatory bowel disease patients and regulates expression of CTLA4 isoforms.
DNA Cell Biol 2010; 29(10):603-10DC

Abstract

We have evaluated functional polymorphism (rs3087243; in literature known also as CTLA4 CT60) in the cytotoxic T lymphocyte antigen 4 (CTLA4) gene, previously associated with several autoimmune diseases, for potential association with inflammatory bowel diseases (IBD). In addition, we investigated correlations between CTLA4 CT60 polymorphism and CTLA4 gene expression in peripheral blood lymphocytes and colon biopsies from IBD patients. We genotyped CTLA4 CT60 polymorphism in 266 healthy control subjects and 481 IBD patients and found statistically lower frequency of CTLA4 CT60 AA genotype in IBD patients (13.72%) compared to control subjects (23.31%; p = 0.001, odds ratio [OR] = 0.504) as well as lower allele frequency of minor A allele in IBD patients (0.346) compared to control subjects (0.461, p < 0.001, OR = 0.623). The association was confirmed with both major forms of IBD, Crohn's disease, and ulcerative colitis (UC), but was slightly stronger in UC patients, particularly when we compared allele frequency of A allele in UC patients (0.299) and control subjects (0.461, p < 0.001, OR = 0.500). We found lower expression of the CTLA4 gene in blood lymphocytes from IBD patients compared to control subjects (p < 0.001) and higher CTLA4 expression in biopsies taken from inflamed part of the colon compared to noninflamed part of the colon (p = 0.021). We found lower expression of soluble CTLA4 isoform than membrane-bound full-length isoform in peripheral blood lymphocytes from IBD patients compared to control subjects (p = 0.010) and in lymphocytes from IBD patients with CTLA4 CT60 GG genotype compared to IBD patients with AA genotype (p = 0.034). Our genotype and gene expression data suggest that CTLA4 plays a role in IBD pathogenesis. Polymorphism CTLA4 CT60 contributes to genetic susceptibility to IBD in Slovenian population and regulates expression of CTLA4 isoforms.

Authors+Show Affiliations

Faculty of Medicine, Center for Human Molecular Genetics and Pharmacogenomics, University of Maribor, Maribor, Slovenia.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20491567

Citation

Repnik, Katja, and Uros Potocnik. "CTLA4 CT60 Single-nucleotide Polymorphism Is Associated With Slovenian Inflammatory Bowel Disease Patients and Regulates Expression of CTLA4 Isoforms." DNA and Cell Biology, vol. 29, no. 10, 2010, pp. 603-10.
Repnik K, Potocnik U. CTLA4 CT60 single-nucleotide polymorphism is associated with Slovenian inflammatory bowel disease patients and regulates expression of CTLA4 isoforms. DNA Cell Biol. 2010;29(10):603-10.
Repnik, K., & Potocnik, U. (2010). CTLA4 CT60 single-nucleotide polymorphism is associated with Slovenian inflammatory bowel disease patients and regulates expression of CTLA4 isoforms. DNA and Cell Biology, 29(10), pp. 603-10. doi:10.1089/dna.2010.1021.
Repnik K, Potocnik U. CTLA4 CT60 Single-nucleotide Polymorphism Is Associated With Slovenian Inflammatory Bowel Disease Patients and Regulates Expression of CTLA4 Isoforms. DNA Cell Biol. 2010;29(10):603-10. PubMed PMID: 20491567.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CTLA4 CT60 single-nucleotide polymorphism is associated with Slovenian inflammatory bowel disease patients and regulates expression of CTLA4 isoforms. AU - Repnik,Katja, AU - Potocnik,Uros, PY - 2010/5/25/entrez PY - 2010/5/25/pubmed PY - 2010/11/5/medline SP - 603 EP - 10 JF - DNA and cell biology JO - DNA Cell Biol. VL - 29 IS - 10 N2 - We have evaluated functional polymorphism (rs3087243; in literature known also as CTLA4 CT60) in the cytotoxic T lymphocyte antigen 4 (CTLA4) gene, previously associated with several autoimmune diseases, for potential association with inflammatory bowel diseases (IBD). In addition, we investigated correlations between CTLA4 CT60 polymorphism and CTLA4 gene expression in peripheral blood lymphocytes and colon biopsies from IBD patients. We genotyped CTLA4 CT60 polymorphism in 266 healthy control subjects and 481 IBD patients and found statistically lower frequency of CTLA4 CT60 AA genotype in IBD patients (13.72%) compared to control subjects (23.31%; p = 0.001, odds ratio [OR] = 0.504) as well as lower allele frequency of minor A allele in IBD patients (0.346) compared to control subjects (0.461, p < 0.001, OR = 0.623). The association was confirmed with both major forms of IBD, Crohn's disease, and ulcerative colitis (UC), but was slightly stronger in UC patients, particularly when we compared allele frequency of A allele in UC patients (0.299) and control subjects (0.461, p < 0.001, OR = 0.500). We found lower expression of the CTLA4 gene in blood lymphocytes from IBD patients compared to control subjects (p < 0.001) and higher CTLA4 expression in biopsies taken from inflamed part of the colon compared to noninflamed part of the colon (p = 0.021). We found lower expression of soluble CTLA4 isoform than membrane-bound full-length isoform in peripheral blood lymphocytes from IBD patients compared to control subjects (p = 0.010) and in lymphocytes from IBD patients with CTLA4 CT60 GG genotype compared to IBD patients with AA genotype (p = 0.034). Our genotype and gene expression data suggest that CTLA4 plays a role in IBD pathogenesis. Polymorphism CTLA4 CT60 contributes to genetic susceptibility to IBD in Slovenian population and regulates expression of CTLA4 isoforms. SN - 1557-7430 UR - https://www.unboundmedicine.com/medline/citation/20491567/CTLA4_CT60_single_nucleotide_polymorphism_is_associated_with_Slovenian_inflammatory_bowel_disease_patients_and_regulates_expression_of_CTLA4_isoforms_ L2 - https://www.liebertpub.com/doi/full/10.1089/dna.2010.1021?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -