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CTLA-4 and TNF-a gene polymorphisms in celiac disease

Introduction: Only 40% of the genetic susceptibility to celiac disease can be attributed to the HLA class II genes. The aim of our study was to determine the possible impact of specific polymorphisms of the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) and tumor necrosis factor-α (TNF-α) genes on the predisposition of celiac disease. Methods: The study included 202 patients with celiac disease and 400 healthy controls. Polymerase chain reaction – restriction fragment length polymorphism (PCR-RFLP) method was used for the identification of TNF-α -238, TNF-α -308, and CTLA4 +49 and CTLA4 CT60 gene polymorphisms. Results: The presence of the CTLA4 +49 and CT60 polymorphisms had no individual impact on the genetic susceptibility to celiac disease. However, the interaction of risk alleles for both CTLA4 polymorphisms showed significant impact on the occurrence of the disease, which was confirmed by the analysis of the haplotype (OR=4.66, p=0.0003). The presence of the TNF-α -308 gene polymorphism strongly correlated with the presence of the disease at the significance level of p<0.001, while TNF-α -238 polymorphism showed no correlation (p>0.05). Examining the interaction of the TNF-α gene -308 and -238 polymorphisms has shown that TNF- -308/-238 AG haplotype represents a risk factor for the development of the disease (OR = 2.53, p <0.0001). The investigation of TNF-α and CTLA4 genes showed the importance of the interaction between TNF-α -308, CTLA4 +49 and CTLA4 CT60 polymorphisms. Patients who are carriers of all three risk alleles also had an associated autoimmune disease in 25.6% of cases. Discussion / Conclusion: The presence of the TNF-α -308 gene polymorphism and the interaction between CTLA4 +49G, CT60G and TNF-α-308A polymorphism affect the predisposition to celiac disease in our patients, but further investigations with larger number of patients are necessary.

Cytotoxic T lymphocyte-associated antigen 4; Coeliac disease; Genetic polymorphism; Tumor necrosis factor-α

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