Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, P.R. China.
DNA Cell Biol. 2012 Sep;31(9):1499-506. doi: 10.1089/dna.2012.1660. Epub 2012 Jun 13.
MicroRNAs (miRNAs) are new prominent gene expression regulators that have critical roles in neural development by regulating synaptic functions, and miRNA biogenesis may play an important role in psychiatric disorders. Despite emerging evidences demonstrating that single-nucleotide polymorphisms in the miRNA processing genes were associated with cancer and cardiovascular disorders, evidences about association between variants of the genes and depression are lacking. This study aims to find the association between miRNA processing gene variants and depression. We genotyped three polymorphisms from three miRNA processing genes in a case-control study including 314 patients and 252 matched healthy controls. The high-resolution melting method was used to genotype the three loci. Frequencies of genotypes and alleles showed significant difference between patients with depression and healthy controls in DGCR8 rs3757 and AGO1 rs636832. An allele frequency was significantly higher in rs3757 and lower in rs636832, respectively. Variant allele of DGCR8 rs3757 was associated with increased risk of suicidal tendency and improvement response to antidepressant treatment, whereas the variant of AGO1 rs636832 showed decreased risk of suicidal tendency, suicidal behavior, and recurrence. Besides allele frequency showed significant difference when compared patients with remission to controls, no significant differences were found in GEMIN4 rs7813 between patients and healthy controls. DGCR8 rs3757 and AGO1 rs636832 were found to have significant association with depression, and GEMIN4 rs7813 did not affect susceptibility to depression. These observations suggested that miRNA processing polymorphisms may affect depression risk and treatment.
微小 RNA（miRNA）是新的重要基因表达调控因子，通过调节突触功能在神经发育中起关键作用，miRNA 的生物发生可能在精神疾病中发挥重要作用。尽管有越来越多的证据表明 miRNA 加工基因中的单核苷酸多态性与癌症和心血管疾病有关，但关于基因变异与抑郁症之间的关联的证据尚缺乏。本研究旨在寻找 miRNA 加工基因变异与抑郁症之间的关联。我们在一项包括 314 例患者和 252 例匹配健康对照的病例对照研究中对三个 miRNA 加工基因的三个多态性进行了基因分型。使用高分辨率熔解曲线法对三个位点进行基因分型。基因型和等位基因频率在 DGCR8 rs3757 和 AGO1 rs636832 中，患者与健康对照组之间存在显著差异。rs3757 的等位基因频率显著升高，而 rs636832 的等位基因频率显著降低。DGCR8 rs3757 的变异等位基因与自杀倾向增加和抗抑郁治疗反应改善相关，而 AGO1 rs636832 的变异等位基因与自杀倾向、自杀行为和复发风险降低相关。除了与对照组相比，缓解期患者的等位基因频率存在显著差异外，在 GEMIN4 rs7813 中未发现患者与健康对照组之间存在显著差异。DGCR8 rs3757 和 AGO1 rs636832 与抑郁症有显著关联，而 GEMIN4 rs7813 不影响抑郁症的易感性。这些观察结果表明，miRNA 加工多态性可能影响抑郁症的风险和治疗。
