Meshkat Marzieh, Mesrian Tanha Hamzeh, Ghaedi Kamran, Meshkat Mahboobeh
Department of Biology, Division of Cellular and Molecular Biology, Nourdanesh University of Meymeh, Meymeh, Isfahan, Iran.
J Genet. 2018 Dec;97(5):1307-1313.
Some of the single-nucleotide polymorphisms in miRNA genes have been studied to date to find their association with the risk of breast cancer (BC). However, no study has been conducted to investigate the association of the rs75598818G>A in BC. In the present study, rs75598818 association with BC in an Iranian population has been investigated, and an analysis was performed to predict the function of rs75598818 polymorphism in BC. The rs75598818 was genotyped in 129 BC patients and 144 healthy women, using the PCR-RFLP method. The frequency of alleles and genotypes were considered to find the associations between rs75598818 alleles/genotypes, and BC risk and pathological characteristics of the patients. Statistical analysis showed that the rs75598818 GA genotype was significantly associated with BC (GA versus GG, OR=0.50, 95% CI: 0.25-0.98, =0.041), highstage BC (stage III/IV versus I/II, GA versus GG, OR=0.27, 95% CI: 0.09-0.81, =0.015), and HER-2 positive status (GA versus GG, OR=19.00, 95% CI: 4.64-77.82, <0.001). Notably, the rs75598818 GA genotype has a negative association pattern since it reduces the risk of BC and high stage BC. Conversely, it increases the risk of HER-2 positivity. Computational results suggested that the rs75598818 polymorphism affects the stability of stem-loop and as a result -3p production that is a potential tumour suppressor. A contribution of the rs75598818 polymorphism to BC had been unexplored before. In the present study, we performed an association study and a bioinformatics approach to evaluate this polymorphism in BC. However, further functional experiments and large-scale association studies with various ethnicities are required to elaborate our findings.
迄今为止，已对一些微小RNA（miRNA）基因中的单核苷酸多态性进行了研究，以探寻它们与乳腺癌（BC）风险的关联。然而，尚未开展研究来调查rs75598818G>A与BC的关联。在本研究中，调查了伊朗人群中rs75598818与BC的关联，并进行了分析以预测rs75598818多态性在BC中的功能。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对129例BC患者和144名健康女性的rs75598818进行基因分型。通过分析等位基因和基因型频率，以找出rs75598818等位基因/基因型与BC风险及患者病理特征之间的关联。统计分析表明，rs75598818的GA基因型与BC显著相关（GA与GG相比，比值比[OR]=0.50，95%置信区间[CI]：0.25 - 0.98，P=0.041）、与晚期BC相关（III/IV期与I/II期相比，GA与GG相比，OR=0.27，95% CI：0.09 - 0.81，P=0.015），以及与HER-2阳性状态相关（GA与GG相比，OR=19.00，95% CI：4.64 - 77.82，P<0.001）。值得注意的是，rs75598818的GA基因型呈现负相关模式，因为它降低了BC和晚期BC的风险。相反，它增加了HER-2阳性的风险。计算结果表明，rs75598818多态性影响茎环的稳定性，从而影响作为潜在肿瘤抑制因子的-3p的产生。此前尚未探索rs75598818多态性对BC的作用。在本研究中，我们进行了关联研究和生物信息学方法来评估BC中的这种多态性。然而，需要进一步的功能实验以及不同种族的大规模关联研究来阐明我们的发现。
