rs372321755 as a new deleterious single nucleotide polymorphism related to NOD2 gene in inflammatory bowel disease
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sajede naghiyan fesharaki,1,* Sajjad Sisakhtnezhad,2
1. Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran
2. Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran
- Introduction: Introduction: Inflammatory bowel diseases (IBD) is a complex and multifactorial condition characterized by chronic gastrointestinal tract inflammation disease. Types of IBD include Crohn's disease (CD) and ulcerative colitis (UC) [1]. Crohn's disease is manifested as patchy transmural inflammatory patterns that affect all layers of the intestinal wall in any portion of the gastrointestinal tract, whereas ulcerative colitis is limited to the innermost layers of the mucosa in the large intestine. CD and UC mainly affect young people, causing bloody diarrhea, abdominal pain, malabsorption, fatigue. Long-lasting inflammation also increases the risk of colorectal cancer in patients with IBD and thus, affects the quality of life of patients [2]. Different studies indicated that NOD2 gene is associated with IBD. The NOD2 protein is active in several types of epithelial cells, including Paneth cells, which are found in the lining of the intestine. These cells help defend the intestinal wall against bacterial infection [3]. Single nucleotide polymorphisms (SNPs) are a type of polymorphism involving variation of a single base pair [4] and when arising in genes can impact on their expression. Therefore, identification and studying the correlation of SNPs with diseases is important for understanding the pathology of them. Also, the SNPs that are associated with target genes may be used as biological markers for prognosis of diseases. Thus, this study carried out to identify the possible new deleterious SNPs in IBD.
- Methods: Methods: Online bioinformatics tools, including NCBI, PROVEAN, SIFT and HOPE, were used for the identification of SNPs associated with NOD2 gene and also for the evaluation of their effects on the protein that is coded by this gene.
- Results: Results: In the present study, various SNPs extracted in the coding region of NOD2 gene. In this regard, the results of SIFT and PROVEAN revealed that rs372321755 is the most significant deleterious SNP in the protein-coding region of NOD2 gene. It also found that rs372321755 induced the substitution of the wild-type A allele with the mutant-type G allele in the NOD2 gene. Moreover, HOPE results indicated that this SNP is cause the Methionine mutation into Valine at the 28nd position of NOD2 protein that this mutation is probably damaging to the protein. In this regard, the wild-type and mutant amino acids differ in size. The mutant residue is smaller, this might lead to loss of interactions.
- Conclusion: Conclusion: This study introduces rs372321755 as a new dangerous SNP that is associated with NOD2 gene and inflammatory bowel disease. The occurrence of this point mutation in NOD2 gene a gene may increase the incidence of IBC by altering the structure of the NOD2 protein.
- Keywords: Keywords: NOD2 gene, Single nucleotide polymorphisms, In silico analysis, rs372321755, Inflammatory
