Martin-Guerrero Idoia, Gutierrez-Camino Angela, Lopez-Lopez Elixabet, Bilbao-Aldaiturriaga Nerea, Pombar-Gomez Maria, Ardanaz Maite, Garcia-Orad Africa
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Odontology, University of the Basque Country, UPV/EHU, Bilbao, Spain.
Hospital Txagorritxu, Vitoria, Spain.
PLoS One. 2015 Mar 20;10(3):e0118905. doi: 10.1371/journal.pone.0118905. eCollection 2015.
Genome wide association studies (GWAS) have identified several low-penetrance susceptibility alleles in chronic lymphocytic leukemia (CLL). Nevertheless, these studies scarcely study regions that are implicated in non-coding molecules such as microRNAs (miRNAs). Abnormalities in miRNAs, as altered expression patterns and mutations, have been described in CLL, suggesting their implication in the development of the disease. Genetic variations in miRNAs can affect levels of miRNA expression if present in pre-miRNAs and in miRNA biogenesis genes or alter miRNA function if present in both target mRNA and miRNA sequences. Therefore, the present study aimed to evaluate whether polymorphisms in pre-miRNAs, and/or miRNA processing genes contribute to predisposition for CLL. A total of 91 SNPs in 107 CLL patients and 350 cancer-free controls were successfully analyzed using TaqMan Open Array technology. We found nine statistically significant associations with CLL risk after FDR correction, seven in miRNA processing genes (rs3805500 and rs6877842 in DROSHA, rs1057035 in DICER1, rs17676986 in SND1, rs9611280 in TNRC6B, rs784567 in TRBP and rs11866002 in CNOT1) and two in pre-miRNAs (rs11614913 in miR196a2 and rs2114358 in miR1206). These findings suggest that polymorphisms in genes involved in miRNAs biogenesis pathway as well as in pre-miRNAs contribute to the risk of CLL. Large-scale studies are needed to validate the current findings.
全基因组关联研究（GWAS）已经在慢性淋巴细胞白血病（CLL）中鉴定出了几个低外显率的易感等位基因。然而，这些研究几乎没有涉及与非编码分子如微小RNA（miRNA）相关的区域。在CLL中已经描述了miRNA的异常，如表达模式改变和突变，这表明它们与疾病的发生有关。如果miRNA的遗传变异存在于前体miRNA和miRNA生物发生基因中，可能会影响miRNA的表达水平；如果存在于靶mRNA和miRNA序列中，则可能改变miRNA的功能。因此，本研究旨在评估前体miRNA和/或miRNA加工基因中的多态性是否会导致CLL的易感性。使用TaqMan Open Array技术成功分析了107例CLL患者和350例无癌对照中的91个单核苷酸多态性（SNP）。在进行错误发现率（FDR）校正后，我们发现了9个与CLL风险具有统计学显著关联的位点，其中7个位于miRNA加工基因中（DROSHA中的rs3805500和rs6877842、DICER1中的rs1057035、SND1中的rs17676986、TNRC6B中的rs9611280、TRBP中的rs784567和CNOT1中的rs11866002），2个位于前体miRNA中（miR196a2中的rs11614913和miR1206中的rs2114358）。这些发现表明，参与miRNA生物合成途径的基因以及前体miRNA中的多态性会增加CLL的发病风险。需要进行大规模研究来验证当前的发现。
