Applied Biochemistry and Biotechnology ( IF 3.1 ) Pub Date : 2021-01-23 , DOI: 10.1007/s12010-021-03489-w Saman Sargazi 1 , Milad Heidari Nia 1 , Fariba Mirani Sargazi 1 , Roghayeh Sheervalilou 1 , Ramin Saravani 1, 2 , Sara Bahrami 1 , Shekoufeh Mirinejad 1 , Ali Alidadi 3
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MiR-143/145 cluster is a novel transcriptional target of many signaling pathways, with variations within this cluster contributed to the risk of multiple diseases. To date, no data regarding the link between miR143/145 cluster polymorphisms and the risk of developing chronic kidney disease (CKD) has been reported. Hence, we aimed to examine such association in a population of Iranian ancestry. In this preliminary study, 276 CKD patients and 300 unrelated age and sex-matched healthy controls were recruited. Genotyping was performed by PCR-RFLP and allele-specific-PCR methods. Computational analyses were performed to predict the potential effects of the variants. Our findings indicated that rs41291957, rs12659504, and rs353292 polymorphisms were positively associated with CKD, while rs4705342 and rs4705343 polymorphisms demonstrated a significant negative association with the disease. Moreover, a significant association was observed between CC + TC and TT genotypes and CKD stages. We found that AACTT, AATTC, AATTT, GATTC, GATTT, and GGCTT haplotypes significantly enhanced the risk of CKD compared with the Grs41291957AArs12659504Crs353292Trs4705342Trs4705343 haplotype. Computational analysis showed that rs353292, rs4705342, and rs4705343 might alter the binding of the transcription factors in this gene cluster. We found that miR-143/145 cluster polymorphisms were associated with CKD risk in a sample of the Iranian population. Replicated studies on different ethnicities are necessary to investigate the association between these promoter variants and clinical outcomes.
Graphical abstract
中文翻译：
功能性 miR143/145 簇变体和单倍型与慢性肾脏病相关：初步病例对照研究和计算分析
MiR-143/145 簇是许多信号通路的新转录靶点，该簇内的变异导致多种疾病的风险。迄今为止，没有关于miR143/145之间联系的数据已经报道了簇多态性和患慢性肾病 (CKD) 的风险。因此，我们旨在检查伊朗血统人群中的这种关联。在这项初步研究中，招募了 276 名 CKD 患者和 300 名不相关的年龄和性别匹配的健康对照。基因分型通过 PCR-RFLP 和等位基因特异性 PCR 方法进行。进行计算分析以预测变体的潜在影响。我们的研究结果表明，rs41291957、rs12659504 和 rs353292 多态性与 CKD 呈正相关，而 rs4705342 和 rs4705343 多态性与该疾病呈显着负相关。此外，在 CC + TC 和 TT 基因型与 CKD 分期之间观察到显着关联。我们发现 AACTT, AATTC, AATTT, GATTC, GATTT,rs41291957A A rs12659504 C rs353292 T rs4705342 T rs4705343单倍型。计算分析表明，rs353292、rs4705342 和 rs4705343 可能会改变该基因簇中转录因子的结合。我们发现miR-143/145簇多态性与伊朗人群样本中的 CKD 风险相关。需要对不同种族进行重复研究，以研究这些启动子变异与临床结果之间的关联。
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