Title : Molecular association between the IL-1RN variable number of tandem repeats polymorphism and helicobacter pylori infection in the Sudanese population
Abstract:
Helicobacter pylori (H. pylori) colonizes the mucus layer of the human stomach in nearly half of the world's population. In Sudan, a variety of sociodemographic factors contribute to a steady increase in the prevalence rate of H. pylori infection, which ranges from 48% to 65.8%, creating a significant public health challenge. As is obvious, there is an increase in demand for H. pylori eradication treatment in Sudan. Additionally, H. pylori is responsible for gastric cancer in approximately tens of millions of patients. Gastric cancer in Sudan represents one of the top causing deaths among cancers with about 686 cases per year and a 2.7 % mortality rate. However, there is no data in Sudan on the relationship between infection susceptibility and severity, and inter-individual genetic variations in IL-1RN, especially VNTR polymorphism which has been reported to increase the susceptibility to H. pylori and gastric cancer risk. Therefore, this observational study aimed to assess the association between the 86 bp VNTR polymorphism of the IL- 1RN gene and the susceptibility to H. pylori infection and gastric cancer in Sudanese patients. A total of 122 gastric biopsies were taken from patients who had been referred for endoscopy from different regions of Sudan. The DNA extraction was performed using the innuPREP DNA Mini Kit. H. pylori infection was Sample Abstract Template investigated by a specific 16S rRNA gene. IL-1RN VNTR polymorphism at intron 2 was genotyped using the PCR method and direct Sanger sequencing for random samples. Differences in frequency distribution among the categorical demographic characteristics of the study population were examined with χ 2 test or Fisher’s test. Associations of the IL- 1RN (86 bp VNTR polymorphism) genotype with H. pylori infection and endoscopic series were assessed by odd ratios (ORs) and 95% confidence intervals (CIs). Differences were considered to indicate statistical significance if P<0.05. Data were analyzed using GraphPad Prism 5 software. Moreover, the association between IL1RN expression and gastric cancer was assessed computationally by using the gene expression profiling interactive analysis (GEPIA) server. In this study, a lack of association was found between IL-1RN 86bp VNTR polymorphism and susceptibility to H. pylori infection (P=0.8412). However, there is a significant association between the carriage of the IL-1RN *2 allele and the risk of gastric cancer in the studied Sudanese population (16.67% versus 50%, P= 0.0086). In silico analysis revealed that the expression of IL-1RN in cancerous gastric tissue was higher than in normal gastric tissue (P<0.01). In conclusion, we found a lack of association between IL-1RN 86bp VNTR polymorphism and susceptibility to H. pylori infection. Independently carriage of the IL-1RN*2 allele contributes significantly to the risk of gastric cancer in the Sudanese population. To the best of our knowledge, this is the first study in Sudan concerning this issue.
Audience Take Away:
• Notwithstanding the relatively small sample size of the study population, our findings show that host genetics can be a useful tool for identifying high-risk individuals among dyspeptic patients.
• Also, our findings underscore the role played by host genetics in gastric carcinogenesis.
• Computational tools were found useful for studying the association between gene expression and gastric cancer
