人微小RNAs成熟体多态与鼻咽癌易感性关系

目的探讨hsa-miR-499(miR499)和hsa-miR-608(miR608)成熟体常见单核苷酸多态位点(rs3746444 T→C和rs4919510 C→G)的遗传变异与中国南方人群鼻咽癌发病关系。方法采用病例对照研究方法,收集原发性鼻咽癌患者612例和正常对照612人,采用TaqMan技术检测miR499和miR608成熟体单核苷酸多态(rs3746444 T→C和rs4919510 C→G)基因型,运用SAS 9.13软件进行非条件logistic回归分析,校正混杂因素影响,分析基因多态与鼻咽癌发病关系。结果 以rs3746444 TT基因型为参照,携带变异基因型(TC+CC)的个体发生鼻咽癌危险增加44%(OR=1.44,95%CI=1.13~1.82);而携带rs4919510(GC+GG)基因型个体发生鼻咽癌风险是携带rs4919510 CC基因型的1.58倍(OR=1.58,95%CI=1.21~2.07);且rs3746444 C和rs4919510 G变异的等位基因个数与鼻咽癌发病风险均存在明显剂量反应关系(P<0.01)。结论 人miR499(rs3746444 T→C)和miR608(rs4919510 C→G)成熟体遗传变异可明显增加南方人群鼻咽癌发病风险。

Association between genetic variations in mature region of microRNAs and risk of nasopharyngeal carcinoma

Objective To investigate the association between the single nucleotide polymorphisms (SNPs) of hsa-miR-499(miR499) and hsa-miR-608(miR608) and the risk of nasopharyngeal carcinoma(NPC) in southern Chinese population.Methods A hospital-based case-control study was conducted among 612 patients with NPC and 612 healthy participants,and the SNPs in mature region of miR499 and miR608 of the participants were genotyped by TaqMan assays.SAS 9.13 software was used to analyze the association between the miR499 as well as miR608 polymorphism and the susceptibility of NPC.Results The distribution frequencies of genotype of miR499(rs3746444 T→C)and miR608(rs4919510 C→G)were significantly different between the cases and controls (P=2.50×10^-4 and 2.71×10^-4,respectively).Compared with homozygous genotype (rs3746444 TT),the risk for NPC was increased by 44% in the carriers of variant genotypes (rs3746444 TC+CC) (adjusted odd ratio[OR]=1.44,95% confidence interval[95%CI]:1.13-1.82).And the carriers of the rs4919510(GC+GG) genotypes had a 1.58 fold risk of NPC compared to those of the rs4919510CC genotype(adjusted OR=1.58,95%CI=1.21-2.07).There was a significantly increased trend in the risk for NPC along with the increased number of variant C allele of rs3746444 as well as variant G allele of rs4919510 (P_trend=2.0×10^-4 and P=0.0001,respectively).Conclusion The findings demonstrate that miR499(rs3746444 T→C)and miR608(rs4919510 C→G) polymorphisms may contribute to an increased risk of NPC.