Association between CTLA-4 gene promoter (49 A/G) in exon 1 polymorphisms and inflammatory bowel disease in the Tunisian population

Abstract

Background/Aim:To investigate the possible association between the polymorphism of the CTLA-4 exon 1 +49 A/G and susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) in the Tunisian population.Methods:The +49 A/G dimorphism was analyzed in 119 patients with CD, 65 patients with UC, and 100 controls by the polymerase chain reaction–restriction fragment length polymorphism method.Results:Significantly higher frequencies of the CTLA-4 +49A allele and A/A homozygous individuals were observed in patients with CD when compared with controls (pc = 0.0023 and pc = 0.0003, respectively). Analysis of CTLA-4 A/G polymorphism with respect to sex in CD showed a significant difference in A/A genotypes between female patients and controls (pc = 0.0001 and pc = 0.038, respectively). There were no differences in the subgroups of patients with CD.Conclusions:Forty-nine A alleles and AA genotype are associated with CD susceptibility in Tunisians. Other genes involved in the T-cell regulation remain strong candidates for IBD susceptibility and require further investigation.

Impact of gut Microbiome alteration in Ulcerative Colitis patients on disease severity and outcome

“…Its downregulation has been linked to autoimmune and lymphoproliferative disorders. The efficiency of therapy and multi-drug resistance in cancer is significantly influenced by multi-drug resistance 1 (MDR1) [ 14 ]. Single-nucleotide polymorphisms in the MDR1 gene, namely rs1045642 C > T, and CTLA-4 gene, primarily rs3087243 G > A and rs231775 G > A, have also been linked to an increased risk of UC [ 14 , 15 ].…”

“…The efficiency of therapy and multi-drug resistance in cancer is significantly influenced by multi-drug resistance 1 (MDR1) [ 14 ]. Single-nucleotide polymorphisms in the MDR1 gene, namely rs1045642 C > T, and CTLA-4 gene, primarily rs3087243 G > A and rs231775 G > A, have also been linked to an increased risk of UC [ 14 , 15 ]. Also CTLA-4 is an inhibitory immune checkpoint that can be accentuated in tumor-infiltrating lymphocytes and colorectal cancer (CRC) cells, facilitating tumor growth and metastasis [ 16 ]; in addition, anticancer immunotherapy by CTLA-4 blockade is accentuated by outgrowth of Bacteroides fragilis with its anticancer properties [ 17 ].…”