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

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

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

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