Çölyak Hastalığı Olan Türk Pediatrik Hastalarda CTLA-4 (rs231775) ve FOXP3 (rs3761548) Genlerinin Polimorfizmleri

Year 2024, Volume: 9 Issue: 3, 365 - 370, 04.10.2024

Abdullah Said Yılmaz , Aslı Eldem , Maşallah Baran , Melek Pehlivan , Tülay Kılıçaslan Ayna , İbrahim Pirim , Mustafa Soyöz

https://doi.org/10.61399/ikcusbfd.1363439

Abstract

Amaç: Çölyak hastalığı, glutenin ince bağırsağa zarar verdiği en yaygın otoimmün hastalıklardan biridir. CTLA-4 ve FOXP3 genleri, immün toleransta önemli bir rol oynamaktadır, bu nedenle bu genlerin polimorfizmlerinin çölyak hastalığı ile ilişkili olabileceği varsayılmaktadır. Çalışmamız çölyak hastalarını sağlıklı kontrol grubu ile karşılaştırarak çölyak hastalığı ile CTLA-4 +49 (rs231775) ve FOXP3 -3279 C/A(rs3761548) polimorfizmleri arasındaki ilişkiyi araştırmayı amaçlamıştır.

Gereç ve Yöntemler: 125 pediatrik çölyak hastasında ve 100 sağlıklı kontrolde CTLA- 4 (rs231775) genindeki +49 A/G ve FOXP3 (rs3761548) genindeki -3279 C/A’nın tek nükleotid polimorfizmleri (SNP), Polimeraz Zincir Reaksiyonu Restriksiyon Fragment Uzunluk Polimorfizmi (PCR-RFLP) yöntemi ile araştırıldı.

Bulgular: CTLA-4 geninin A ve G alelleri çölyak hasta grubunda kontrol grubuna göre daha sık bulundu. Ayrıca FOXP3 geninin A ve C alelleri çölyak hastalarında sağlıklı kontrollere göre daha sık bulundu. CTLA-4 +49 A/G ve FOXP3 -3279 C/A için genotip veya alel frekansına dayalı olarak istatistiksel olarak anlamlı bulunmamıştır (p>0,05). Risk aleli analiz edildiğinde, FOXP3 gen polimorfizminin CD hastalarında anlamlı bulunmuştur (p<0,05).

Sonuç: Türk pediatrik çölyak hastalarında CTLA-4 ve FOXP3 polimorfizmlerini değerlendiren ilk çalışmadır. HLA dışı genlerin polimorfizmlerinin önemi, HLA genlerinde olduğu gibi çölyak riski ile ilişkilendirilebilir, ancak daha ileri çalışmalar yapılmalıdır.

Keywords

Çölyak hastalığı, CTLA-4, FOXP3, Gen polimorfizmi

Supporting Institution

İKÇÜ BAP

Project Number

2020-TYL-SABE-003

Thanks

-

Polymorphisms of CTLA-4 (rs231775) and FOXP3 (rs3761548) Genes with Celiac Disease in Turkish Pediatric Patients

Abstract

Objective: Celiac disease (CD) is one of the most common autoimmune disorders in which gluten damages the small intestine. The CTLA-4 and FOXP3 genes play an important role in immune tolerance, so it is hypothesized that polymorphisms of these genes may be related to celiac disease. Our study aimed to investigate the associated with celiac disease and the CTLA-4 +49 A/G (rs231775) and FOXP3 -3279 C/A (rs3761548) polymorphisms by comparing celiac disease patients with a healthy control group.

Material and Methods: The single nucleotide polymorphisms (SNP) of +49 A/G in CTLA-4 (rs231775) gene and -3279 C/A in FOXP3 (rs3761548) gene were studied by Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) method in 125 pediatric celiac patients and 100 healthy controls.

Results: The A and G alleles of the CTLA-4 gene were found more frequently in the celiac patient group than in the control group. In addition, the A and C alleles of the FOXP3 gene were found more frequently in celiac disease patients than in healthy controls. There were no statistically significant results for the two polymorphisms CTLA-4 +49 A/G and FOXP3 -3279 C/A based on genotype or allele frequency (p > 0.05). When analyzing the risk allele, the FOXP3 gene polymorphism -3279 C/A proved to be significant in CD patients (p<0.05).

Conclusion: This is the first study to evaluate the CTLA-4 and FOXP3 polymorphisms in Turkish pediatric celiac patients. The significance of polymorphisms of non-HLA genes may be associated with celiac risk as that of HLA genes, but further studies should be performed.

Keywords

Celiac disease, CTLA-4, FOXP3, gene polymorphism

Ethical Statement

The Ethics Committee approved the study by Decision No. 34, dated February 06, 2019, and the parents of the patients were informed and informed consent forms were signed

Supporting Institution

Izmir Katip Celebi University Scientific Research Projects

Project Number

2020-TYL-SABE-003

Thanks

none

References

• Eldem, A., Ayna, T. K., Baran, M., Soyoz, M., & Pirim, İ. Determination of High-Resolution HLA-DQB1 Suballeles and IL-17 Polymorphisms in Turkish Pediatric Patients. Journal of Pediatric Genetics. 2021; 11(3): 192–197
• Lundin, K. E., & Wijmenga, C. Coeliac disease and autoimmune diseasegenetic overlap and screening. Nature reviews Gastroenterology & hepatology. 2015;12(9), 507-515.
• Serena, G., Lima, R., & Fasano, A. Genetic and environmental contributors for celiac disease. Current Allergy and Asthma Reports.2019; 19(9), 1-10.
• Uhrberg, M., Parham, P., & Wernet, P. Definition of gene content for nine common group B haplotypes of the Caucasoid population: KIR haplotypes contain between seven and eleven KIR genes. Immunogenetics.2002; 54(4), 221-229.
• Song, G. G., Kim, J. H., Kim, Y. H., & Lee, Y. H. Association between CTLA- 4 polymorphisms and susceptibility to Celiac disease: a meta-analysis. Human Immunology. 2013;74(9), 1214-1218.
• Scazzone, C., Agnello, L., Lo Sasso, B., Salemi, G., Gambino, C. M., et.al. Foxp3 and gata3 polymorphisms, vitamin d3 and multiple sclerosis. Brain Sciences, 2021;11(4), 415.
• Hosseini, A., Shanehbandi, D., Estiar, M. A., Gholizadeh, S., Khabbazi, A., et.al. A single nucleotide polymorphism in the FOXP3 gene associated with Behcet’s disease in an Iranian population. Clin Lab.2015; 61(12), 1897-903.
• Fathima, N., Narne, P., & Ishaq, M. Association and gene–gene interaction analyses for polymorphic variants in CTLA-4 and FOXP3 genes: role in susceptibility to autoimmune thyroid disease. Endocrine. 2019; 64(3), 591-604.
• Husby, S., Koletzko, S., Korponay-Szabo, I., Kurppa, K., Mearin, M. L., et.al. European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for Diagnosing Coeliac Disease 2020. Journal of pediatric gastroenterology and nutrition. 2020; 70(1), 141–156.
• Chatrabnous N, Ghaderi A, Ariafar A, et al. Serum concentration of interleukin- 35 and its association with tumor stages and FOXP3 gene polymorphism in patients with prostate cancer. Cytokine. 2019;113:221– 227.
• Murad, H., Jazairi, B., Khansaa, I. et al. HLA-DQ2 and -DQ8 genotype frequency in Syrian celiac disease children: HLA-DQ relative risks evaluation. BMC Gastroenterol.2018; 18, 70.
• Chen, Z., Fei, M., Fu, D., Zhang, L., Ma, Y., Wang, Y., ... & Wang, X. Association between cytotoxic T lymphocyte antigen-4 polymorphism and type 1 diabetes: a meta-analysis. Gene. 2013;516(2), 263-270.
• Tang, M. J., & Zhou, Z. B. Association of the CTLA-4+ 49A/G polymorphism with rheumatoid arthritis in Chinese Han population. Molecular biology reports. 2013; 40(3), 2627-2631.
• Lee MG, Bae SC, Lee YH. Association between FOXP3 polymorphisms and susceptibility to autoimmune diseases: A meta-analysis. Autoimmunity. 2015;48(7): 445–52.
• Mora, B., Bonamico, M., Indovina, P., Megiorni, F., Ferri, M., Carbone, M. C., ... & Mazzilli, M. C. CTLA-4+ 49 A/G dimorphism in Italian patients with celiac disease. Human immunology. 2003;64(2), 297-301.
• Abdullah, S. H., & Al-Badran, A. I. (2022). The CTLA4 Polymorphism And Incidence Of Celiac Disease In Thi-Qar Province-South Of IRAQ. Ann. For. Res, 65(1), 8282-8294.
• Bjornvold M, Amundsen SS, Stene LC, et al. FOXP3 polymorphisms in type 1 diabetes and coeliac disease. J Autoimmun. 2006;27(2): 140–4.
• Li, H. N., Li, X. R., Du, Y. Y., Yang, Z. F., & Lv, Z. T. The association between Foxp3 polymorphisms and risk of Graves' disease: a systematic review and meta-analysis of observational studies. Frontiers in endocrinology. 2020; 11, 392.
• Shen, Z., Chen, L., Hao, F., Wang, G., Fan, P., & Liu, Y. Intron‐1 rs3761548 is related to the defective transcription of Foxp3 in psoriasis through abrogating E47/c‐Myb binding.2010; Jan;14(1-2):226-41