Genetic Polymorphisms of miR-146a and miR-27a, H. pylori Infection, and Risk of Gastric Lesions in a Chinese Population

Abstract

BackgroundMicroRNAs (miRNAs) have been implicated in various human diseases. Single nucleotide polymorphisms (SNPs) in inflammation-related miRNA may play an important role in Helicobacter pylori (H. pylori)-induced gastric lesions. To evaluate the associations between miRNA SNPs, H. pylori and gastric lesions, a population-based study was conducted in Linqu County, China.Methodology/Principal FindingsBased on serum miRNA array conducted in this population, two SNP loci (miR-146a rs2910164: G>C and miR-27a rs895819: T>C) were determined by polymerase chain reaction-restriction fragment length polymorphism in 2,380 participants with diverse gastric lesions. Using participants with superficial gastritis and mild chronic atrophic gastritis as the reference group, we found that rs2910164 CC carriers had a significantly increased risk of intestinal metaplasia [adjusted odds ratio (OR), 1.42; 95% confidence interval (CI), 1.03–1.97] and dysplasia (OR, 1.54; 95% CI, 1.05–2.25) compared to GG carriers, whereas no significant association was observed for rs895819. Stratified analysis by H. pylori infection indicated that rs2910164 C allele was associated with an increased risk of intestinal metaplasia and dysplasia only among individuals infected with H. pylori (CC vs. GG: OR, 1.53; 95% CI, 1.12–2.08, P for trend = 0.004). Participants who simultaneously carried variant alleles and H. pylori infection were more likely to develop intestinal metaplasia and dysplasia, although the interaction between genetic variants and H. pylori infection was not significant (P for interaction = 0.35 for rs2910164 and 0.92 for rs895819).Conclusions/SignificanceThese findings suggest that miR-146a rs2910164 polymorphism may contribute to the evolution of H. pylori-associated gastric lesions in this high-risk population.

Gene Polymorphisms of Micrornas in Helicobacter pylori-Induced High Risk Atrophic Gastritis and Gastric Cancer

“…Song et al found that CC carriers of rs2910164 had a significantly increased risk of IM (OR - 1.42) and dysplasia (OR - 1.54) compared to GG carriers [12]. A similar observation was made in another study where combined effect of miR-146a (rs2910164) G/G and TLR4 SNP on the increased risk of severe AG among Japanese subjects was observed [18].…”

“…Another study showed a significantly increased risk of GC (OR - 1.48) for miR-27a SNP and further functional analyses indicated that variant genotypes might be responsible for elevated miR-27a levels and reduced ZBTB10 mRNA levels [16]. In contrast, a study including 2,380 participants with diverse gastric lesions did not find an increased risk of gastric IM or dysplasia for rs895819 [12]. A meta-analysis summarizing the findings of different case-control studies revealed that rs895819 polymorphism was significantly associated with decreased risks of cancer in white, but not in Asians [31].…”

Association of a Pre-miR-27a Polymorphism with Cancer Risk: an Updated Meta-analysis

“…Out of the Twenty-five, seven articles were pooled analysis, commentary and review papers (Wang et al, 2012;Yang and Burwinkel, 2012;Ma et al, 2013;Wang et al, 2013;Xu et al, 2013b;Zhong et al, 2013;Chen et al, 2014), and four reports were cancer biology experimental studies (Hirota et al, 2012;Jahid et al, 2012;Zanetti et al, 2012;Yuan et al, 2013). Three studies were excluded given that they did not include controls (Yoon et al, 2012;Xu et al, 2013a), or reported non-cancer disease (Song et al, 2013). We also included five eligible articles by manual searching (Li, 2011;Zhang, 2011;Zhang, 2012;Xu et al, 2013b;Kupcinskas et al, 2014), in which the study by Li et al included two independent case-control studies (Li, 2011) and the pooled analysis by Xu et al included one unpublished paper with efficient case-control study data (Xu et al, 2013b).…”

Helicobacter pylori and Gastric Cancer

“…Among these are cytokine genes involved in the adaptive immune system [98,99,100] and pattern recognition factors initiating the innate immune system [101,102]. Furthermore, variation of genes encoding for proteases [103], xenobiotic metabolism enzymes [104], cell cycle regulators [105,106], mucins [107], HLA molecules [108], transcription factors [109], DNA repair enzymes [105,110,111], and micro-RNAs [112] has been reported to bear an increased risk for gastric cancer. Besides a ‘single gene' approach, also pathway-related pattern searches can be performed to allow a broader assessment of the pathobiological background [113].…”