【摘要】 目的 探讨miR-449a rs112310158基因多态性与胃癌易感性的关系。方法 共纳入448例胃癌患者和452例健康对照者。miR449a rs112310158基因型检测采用聚合酶链反应结合直接测序方法。miR-449a表达水平检测采用荧光定量PCR方法。此单核苷酸多态性位点功能由RT-PCR和免疫组化试验验证。结果 相对于对照组,胃癌病例组在吸烟者(OR=1.345,95%CI=1.028~1.761)、饮酒者(OR=1.910,95%CI=1.465~2.490)、有肿瘤家族史者(OR=4.178,95%CI=1.554~11.231)、幽门螺杆菌感染率较高者(OR=1.428,95%CI=1.098 1.857),差异均具有统计学意义。相较AA基因型,GG基因型显著增加胃癌的发病风险(OR=2.542,95%CI:1.304~4.954,P=0.005)。相较于A等位基因,携带G等位基因的个体罹患胃癌的风险升高(OR=1.279,95%CI:1.012~1.617,P=0.043)。GG型患者比AA型患者miR-449a表达水平下降。与AA基因型相比,miR-449a靶基因PRKCE在GG基因型胃癌患者中有更高的表达。结论 该研究发现miR-449a rs112310158是胃癌的遗传易感因素之一。更多还原

【Abstract】 Objective To investigate the relationship of a genetic variant at miR-449 a and the risk of gastric cancer.Methods The polymerase chain reaction(PCR) and direct sequencing were used to genotype sequence variants of miR-449 a in 448 gastric cancer(GC) cases and 452 controls.The miR-449 a levels were measured by quantitative real-time PCR.The function of rsll2310158 was confirmed by RT-PCR and immunohistochemistry assay.Results GC cases were more likely to be cigarette smokers(OR=1.345,95%CI= 1.028 ~1.761) and alcohol drinkers(OR =.1.910,95%CI= 1.465~2.490),had cancer history in the first relatives(OR=4.178,95%CI=1.554 ~11.231),and have higher infection rate of Helicobacter pylori(OR=l.428,95%CI=1.098 ~ 1.857).Individuals carrying the GG genotypes for the rsll2310158 were associated significantly with increased risk of gastric cancer comparing with those carrying wild-type homozygous A A genotypes(OR=2.542,95%CI:1.304~4.954,P = 0.005).Furthermore,the G allele increased the risk of occurrence of gastric cancer compared to the A allele(OR=l.279,95%CI:l.012 ~ 1.617,P = 0.043).rsll2310158 was associated with the expressionof miR-449 a and its target gene.Conclusion A genetic variant at miR-449 a may play an important role in the development of gastric cancer.更多还原