Functional gene polymorphisms and expression alteration of selected microRNAs and the risk of various gastric lesions in Helicobacter pylori-related gastric diseases

Abstract

Background:Helicobacter pylori (Hp) persistent infection is an important pathogenic factor for a series of chronic gastric diseases from chronic gastritis to gastric cancer. Genetic and epigenetic abnormalities of microRNAs may play a vital role in the pathological evolution of gastric mucosa in Helicobacter pylori-related gastric diseases (HPGD). This study aimed to investigate the relationship between miR-146a, miR-196a2, miR-149, miR-499 and miR-27a gene single nucleotide polymorphisms (SNPs) and their expressions with pathological changes in gastric mucosa, and to further analyze the interactions between SNPs and Hp.Methods: Subjects in this study included patients diagnosed with HPGD and healthy controls. MiR-146a rs2910164, miR-196a2 rs11614913, miR-149 rs2292832, miR-499 rs3746444 and miR-27a rs895819 were genotyped by direct sequencing. Fluorescence quantitative PCR was used to detect microRNA expressions. Gene-gene and gene-environment interactions were evaluated by multifactor dimensionality reduction (MDR) method.Results: we found that frequency distribution of miR-196a2 rs11614913 CT genotype in gastric precancerous lesion (GPL) group and gastric cancer (GC) group was significantly higher than normal control (NOR) group [adjusted OR = 6.16, 95%CI (1.46–26.03); adjusted OR = 11.83, 95%CI (1.65–84.72), respectively]. CT genotype and C allele of miR-27a rs895819 were associated with increased risk of GC [adjusted OR = 10.14, 95%CI (2.25–45.77); adjusted OR = 3.71, 95%CI(1.46–9.44), respectively]. The MDR analysis results showed that the interaction between miR-196a2 rs11614913 and Hp was associated with the risk of GPL (p = 0.004). Meanwhile, the expression level of miR-196a2 in GC group was significantly higher than NOR, chronic inflammation (CI) and early precancerous lesion (EPL) groups among Hp-positive subjects. And expressions of miR-499 and miR-27a in GC group were both higher than EPL group. Also, miR-27a expression in GC group was higher than CI and gastric atrophy (GA) groups.Conclusion: miR-196a2 rs11614913 and miR-27a rs895819 may affect the genetic susceptibility to GPL or GC. MiR-196a2 rs11614913 and Hp have a synergistic effect in the occurrence and development of GPL. The up-regulation of miR-499, miR-196a2 and miR-27a expression caused by Hp infection may be an important mechanism of gastric carcinogenesis.

Non-Coding RNA as Biomarkers and Their Role in the Pathogenesis of Gastric Cancer—A Narrative Review

“…The authors demonstrated that the C allele of the mRNA-499 rs3746444 T>C SNP increased susceptibility to GC. Several other SNPs-miR-196a2 rs11614913, miR-27a rs895819, miR-499 rs3746444, miR-27a rs895819, miR-4427 rs701213, miR-548j rs4822739, miR-938 rs12416605, miR-4274 rs1553867776, miR-3175 rs1439619, miR-6891 rs6149511, miR-8084 rs404337, miR-4719 rs7500280 and miR-34b/c rs4938723-have been associated with an increased or decreased susceptibility to GC [58][59][60][61][62]. Interestingly, SNPs have been combined with other parameters to evaluate the correlation with gastric malignancy.…”

“…Interestingly, SNPs have been combined with other parameters to evaluate the correlation with gastric malignancy. Interestingly, the combination of the miR-196a2 rs11614913 polymorphism and H. pylori seems to be associated with gastric precancerous lesions [58].…”