[摘要] 目的：探讨青岛地区汉族人群lncRNA H19 单核苷酸多态性（SNP）与胃癌和EBV相关胃癌(EBVaGC)易感性的关系。方法：收集青岛地区汉族人群2015 年1 月至2018 年10 月青岛大学附属医院经病理科确诊为胃癌的新鲜组织或陈旧的石蜡包埋胃癌组织病理标本共225 例，为胃癌组；依据原位杂交法对EBV编码的小分子非多聚腺苷酸(EBER1)转录检测结果再将胃癌组分为2 亚组：EBVaGC 组70 例，EBVnGC组155 例；同时选择青岛大学附属医院门诊健康体检者200 例为对照组。提取EBVaGC、EBVnGC 组织及健康人群外周血标本的DNA，根据HaploView 软件常规设置原则（MAF>0.05；r2>0.8）筛选出rs217727、rs2735971、rs2839698 和rs3741216 四个H19 的TagSNPs。利用Taq-Man MGB 等位基因分型试剂盒对各SNP位点基因进行基因分型，并进行基因多态性检测。结果：所取标本的H19 SNPs 均符合Hardy-Weinberg 平衡。与对照组比较，胃癌组H19 rs217727位点TT 基因型的发病风险显著增加(χ2=9.073, P=0.003, OR=1.999, 95% CI=1.271～3.143)，等位基因T 的分布也明显增高(χ2=13.475, P=0.001, OR=1.661, 95% CI=1.266～2.180)；H19 rs2839698 位点TC、CC基因型人群可显著增加胃癌的发病风险(χ2=9.407,P=0.002; χ2=6.517, P=0.011)，携带C等位基因人群罹患胃癌的风险明显增加(χ2=6.163, P=0.013, OR=1.417, 95% CI=1.076~1.867;χ2=9.542, P=0.02, OR=2.070, 95% CI=1.298~3.302)。但胃癌组H19 rs2735971 和rs3741216 位点基因多态性与对照组比较差异不明显（均P>0.05）；EBVaGC 和EBVnGC 组中H19 的4 个位点基因多态性分布差异均无统计学意义（均P>0.05）。结论：H19 rs217727、rs2839698 基因多态性可能与胃癌发病风险有关，携带TT 基因型C等位基因和人群胃癌的发病风险明显升高；H19 SNP的多态性与EBVaGC的发病风险无明显相关。

[Abstract] Objective: To evaluate the potential associations between the single nucleotide polymorphisms (SNPs) of lncRNA H19 genes and the susceptibility to gastric cancer (GC), especially to EBV-associated gastric cancer (EBVaGC) in Han population in Qingdao.Methods: 225 cases of pathologically confirmed fresh gastric cancer tissues or paraffin embedded gastric cancer tissues during January 2015 and October 2018 were collected from Affiliated Hospital of Qingdao University, as GC group; in the meanwhile, 200 healthy people underwent physical examination at Outpatient were collected as control. The 225 cases of cancer tissues were assigned into two groups according to the transcription result of EBV-encoded small molecule non-polyadenylation (EBER 1) by In situ hybridization:EBVaGC group (70 cases) and EBVnGC group (155 cases). DNA was extracted from the tissues of two groups and peripheral blood of healthy participants. According to the general setting of HaploView software (MAF>0.05, r2>0.8), four TagSNPs (rs217727, rs2735971,rs2839698 and rs3741216) of H19 were screened. Genotyping of each SNP locus was carried out by using Taq-Man MGB allele typing kit, and the gene polymorphisms were examined. Results: H19 SNPs of collected tissue samples were in accordance with the Hardy-Weinberg equilibrium. Compared with control group, patients carrying TT genotype of H19 rs217727 loci had significantly increased susceptibility to gastric cancer (χ2=9.073, P=0.003, OR=1.999, 95% CI=1.271-3.143), so did the T allele (χ2=13.475, P=0.001, OR=1.661, 95% CI=1.266-2.180). In contrast, patients carrying TC and CC genotype of rs2839698 loci had significantly increased susceptibility to gastric cancer (χ2=9.407, P=0.002; χ2=6.517, P=0.011), and patients carrying C allele had obviously increased susceptibility to GC (χ2=6.163, P=0.013, OR=1.417, 95%CI=1.076-1.867; χ2=9.542, P=0.02, OR=2.070, 95%CI=1.298-3.302). As for the rs2735971 and rs3741216, there was no significant difference between the GC group and the control group (all P>0.05). The distribution of 4 H19 SNPs showed no statistical difference in both EBVaGC group and EBVnGC group (all P>0.05). Conclusion: There was an association between H19 gene polymorphism (rs217727 and rs2839698) and gastric carcinoma; patients carrying the TT genotype of rs217727 and C allele of rs2839698 may increase the risk of gastric carcinoma. No significant association was observed between H19 SNP polymorphism and risk of EBVaGC.

国家自然科学基金资助项目（No.30970157）；山东省自然科学基金资助项目（No.ZR2011CM016）