Polymorphisms in microRNA target sites influence susceptibility to schizophrenia by altering the binding of miRNAs to their targets
Polymorphisms in microRNA target sites influence susceptibility to schizophrenia by altering the binding of miRNAs to their targets
复制标题
DOI：
10.1016/j.euroneuro.2012.12.002
复制
发表时间：
2013-10-01
影响因子：
5.6
通讯作者：
Zhao, X. Z.
中科院分区：
文献类型：
--
作者：
Gong, Yunguo;Wu, Chao N.;Zhao, X. Z.
基因 3' 非翻译区 (3' UTR) 中的单核苷酸多态性 (SNP) 可能会影响 miRNA 与信使 RNA 的结合，并增加疾病风险。修饰 3' UTR 中 miRNA 结合的 SNP 是否参与精神分裂症相关基因仍不清楚。我们从 425 个精神分裂症候选基因的 3' UTR 中选择了 803 个 SNP。通过 miRNA 结合的吉布斯自由能识别潜在的目标 SNP。文献中一些 SNP 与精神分裂症或其他相关神经系统疾病有关。在中国汉族队列中开展了一项病例对照研究，研究了之前未报道过对任何疾病具有显着意义的 9 个 SNP。我们发现 rs3219151（C>T，GABRA6）显示精神分裂症风险显着降低（OR=0.8121，p=0.008，p（调整）=0.03）。此外，选择先前在几篇参考文献中报道的两个假定的目标 SNP，rs165599 (COMT) 和 rs10759 (RGS4) 进行荧光素酶测定分析，以确定它们对 miRNA 结合的修饰。我们发现 miR-124 显示出显着抑制 3' UTR 与 rs10759-C 等位基因的 RGS4 mRNA 的结合（p
Single nucleotide polymorphisms (SNPs) in 3' untranslated regions (3' UTRs) of genes may affect miRNA binding to messenger RNA and contribute to the risk of disease. Whether the SNPs that modify miRNA binding in the 3' UTR are involved in schizophrenia-related genes remains unclear. We selected 803 SNPs from the 3' UTRs of 425 candidate genes for schizophrenia. The potential target SNPs were recognized by Gibbs free energy of miRNA binding. Some SNPs were associated in the literature with schizophrenia or other related neurological diseases. A case-control study of nine SNPs not previously reported as significant in any disease was carried out in a Chinese-Han cohort. We found that rs3219151 (C>T, GABRA6) showed significant decreased risk for schizophrenia (OR=0.8121, p=0.008, p(adjust)=0.03). Further, two putative target SNPs, rs165599 (COMT) and rs10759 (RGS4) reported in several references previously, were selected for analysis by luciferase assay to determine their modification to miRNA binding. We found that miR-124 showed significantly repressed 3' UTR binding to RGS4 mRNA from the rs10759-C allele (p