Department of Medicine II, Saarland University Hospital, Homburg 66421, Germany.
Hepatobiliary Pancreat Dis Int. 2012 Aug 15;11(4):412-7. doi: 10.1016/s1499-3872(12)60200-8.
Micro-RNAs (miRNAs) are small, non-coding RNA species considered to fine-tune basic cellular functions by modulating target gene translation and/or mRNA stability. A common G/C polymorphism (rs2910164) in the precursor (pre-) miR-146a gene engaged in NF-κB signaling and apoptosis pathways has been reported to modulate the genetic risk of hepatocellular carcinoma by increased G-allelic production of mature miR-146a. We investigated rs2910164 in a large European-based cholangiocarcinoma (CCA) cohort.
We recruited 182 CCA patients and 350 controls in three academic medical centers. Genotyping for rs2910164 was performed by PCR-based assays with 5'-nuclease and fluorescence detection. Genotype frequencies were tested for consistency with the Hardy-Weinberg equilibrium using an exact test; allelic and genotypic differences between the patients and controls were assessed by the Chi-square test and Armitage's trend test. Exploratory subgroup analyses included gender, tumor localization (extra- versus intrahepatic CCA) and early-onset CCA.
Genotype distributions were consistent with the Hardy-Weinberg equilibrium. No significant differences in either allele or genotype distributions were detected between the CCA and control groups or the respective subgroups investigated. However, there was a trend for a protective effect of the heterozygous single-nucleotide polymorphism state GC, as indicated by an underrepresentation in the CCA group in general (29% vs 35%; P=0.18) and, in particular, for extrahepatic tumor sites (26% vs 35%; OR=0.67; 95% CI, 0.43-1.02; P=0.065).
Our data do not support a prominent contribution of the pre-miR-146a sequence variant in the genetic predisposition to CCA. However, current studies functionally characterizing rs2910164 have proposed that distinct repertoires of target genes are addressed by genotype-specific mature miR-146a species. Given the detected trend towards a potentially protective role of GC heterozygosity, a subtle modulation of genetic CCA risk by the pre-miR-146a GC genotype may exist and should be evaluated further.
微小 RNA（miRNA）是一类小型非编码 RNA 分子，被认为通过调节靶基因翻译和/或 mRNA 稳定性来精细调节基本细胞功能。先前的研究报道，miR-146a 基因前体（pre-）miR-146a 中的一个常见 G/C 多态性（rs2910164）参与 NF-κB 信号转导和细胞凋亡途径，通过增加成熟 miR-146a 的 G 等位基因产生，调节肝细胞癌的遗传风险。我们在一个大型欧洲胆管癌（CCA）队列中研究了 rs2910164。
我们在三个学术医疗中心招募了 182 名 CCA 患者和 350 名对照。通过基于 PCR 的 5'-核酸酶和荧光检测方法进行 rs2910164 基因分型。使用确切检验检验基因型频率是否符合 Hardy-Weinberg 平衡；使用卡方检验和 Armitage 趋势检验评估患者和对照组之间的等位基因和基因型差异。探索性亚组分析包括性别、肿瘤定位（肝外与肝内 CCA）和早发性 CCA。
基因型分布符合 Hardy-Weinberg 平衡。CCA 组和对照组或各自的亚组之间，等位基因或基因型分布均无显著差异。然而，杂合单核苷酸多态性状态 GC 存在保护性作用的趋势，一般情况下 CCA 组中 GC 基因型的代表率较低（29%对 35%；P=0.18），特别是肝外肿瘤部位（26%对 35%；OR=0.67；95%CI，0.43-1.02；P=0.065）。
我们的数据不支持 pre-miR-146a 序列变异在 CCA 的遗传易感性中起主要作用。然而，目前研究通过功能特征分析 rs2910164，提出特定的 miR-146a 成熟体物种的基因型特异性靶基因谱。鉴于检测到的 GC 杂合性可能具有潜在保护作用的趋势，pre-miR-146a GC 基因型可能对 CCA 的遗传风险有微妙的调节作用，应进一步评估。
