miRSNPs of miR1274 and miR3202 Genes that Target MeCP2 and DNMT3b Are Associated with Lung Cancer Risk: A Study Conducted on MassARRAY Genotyping.

C. Ozbayer, I. Degirmenci, Derya Ustuner, Guntulu Ak, F. Saydam, E. Çolak, H. Gunes, M. Metintaş
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Abstract

Genetic variants of miRNAs that target DNMTs and MBDs involved in DNA methylation were scanned with current databases, and 35 miRSNPs in 22 miRNA genes were identified. The aim of the study was to determine the association between these variants of miRNA genes and lung cancer (LC). DNA samples were isolated from blood samples and genotyped using a Sequenom MassARRAY System. An association between the rs188912830 gene variant of miR3202 that targets the MeCP2 protein and LC was indicated in both subtypes. The presence of the C-allele in patients with LC and its subtypes was significantly lower, and the absence of the C-allele was determined to increase the risk of LC by 7,429-times compared to the presence (p=0,010). The rs318039 gene variant of miR1274 that targets DNMT3b was found to be associated with LC subtypes. When allele distributions were compared, the numbers of individuals with the C-allele were significantly lower in the NSCLC and SCLC groups. No significant associations were found for the rs72563729 variant of the miR200b gene that targets DNMT3a or for the rs145416750 variant of the miR513c gene that targets TRDMT1. The other 33 variants were found to be ancestral genotypes. Consequently, rs188912830 and rs318039 variations were associated with LC subtypes. Importantly, this study is the first to indicate the functional characterisation of miRSNPs of genes that target DNA methylation.
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靶向MeCP2和DNMT3b的miR1274和miR3202基因的mirsnp与肺癌风险相关:MassARRAY基因分型研究
利用现有数据库扫描了参与DNA甲基化的靶向dnmt和MBDs的miRNA的遗传变异,鉴定出22个miRNA基因中的35个mirsnp。该研究的目的是确定这些miRNA基因变异与肺癌(LC)之间的关系。从血液样本中分离DNA样本,并使用Sequenom MassARRAY系统进行基因分型。miR3202靶向MeCP2蛋白的rs188912830基因变异与LC在两种亚型中均存在关联。LC及其亚型患者中c等位基因的存在明显较低,与存在相比,确定c等位基因缺失使LC的风险增加7,429倍(p=0,010)。miR1274靶向DNMT3b的rs318039基因变异被发现与LC亚型相关。当比较等位基因分布时,具有c等位基因的个体数量在NSCLC和SCLC组中明显较低。靶向DNMT3a的miR200b基因的rs72563729变异和靶向TRDMT1的miR513c基因的rs145416750变异没有发现显著的相关性。其他33个变异被发现是祖先的基因型。因此,rs188912830和rs318039变异与LC亚型相关。重要的是,这项研究首次指出了靶向DNA甲基化的基因的mirsnp的功能特征。
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