Department of Genetic Psychology, Faculty of Psychology, Ruhr-University Bochum, Universitätsstraße 150, 44801 Bochum, Germany.
Department of Psychosomatic Medicine and Psychotherapy, LWL University Hospital, Ruhr University Bochum, 448791 Bochum, Germany.
Genes (Basel). 2023 Jun 21;14(7):1312. doi: 10.3390/genes14071312.
MicroRNAs are tissue-specific expressed short RNAs that serve post-transcriptional gene regulation. A specific microRNA can bind to mRNAs of different genes and thereby suppress their protein production. In the context of the complex phenotype of fibromyalgia, we used the Axiom miRNA Target Site Genotyping Array to search genome-wide for DNA variations in microRNA genes, their regulatory regions, and in the 3'UTR of protein-coding genes. To identify disease-relevant DNA polymorphisms, a cohort of 176 female fibromyalgia patients was studied in comparison to a cohort of 162 healthy women. The association between 48,329 markers and fibromyalgia was investigated using logistic regression adjusted for population stratification. Results show that 29 markers had -values < 1 × 10, and the strongest association was observed for rs758459 (-value of 0.0001), located in the gene which is targeted by hsa-miR-130a-3p. Furthermore, variant rs2295963 is predicted to affect binding of hsa-miR-1-3p. Both microRNAs were previously reported to be differentially expressed in fibromyalgia patients. Despite its limited statistical power, this study reports two microRNA-related polymorphisms which may play a functional role in the pathogenesis of fibromyalgia. For a better understanding of the disease pattern, further functional analyses on the biological significance of microRNAs and microRNA-related polymorphisms are required.
微小 RNA 是组织特异性表达的短 RNA，可在转录后调控基因。特定的微小 RNA 可以与不同基因的 mRNAs 结合，从而抑制其蛋白质的产生。在纤维肌痛复杂表型的背景下，我们使用 Axiom miRNA 靶位基因分型阵列，在 microRNA 基因、其调控区域和蛋白编码基因的 3'UTR 中，搜索全基因组的 DNA 变异。为了鉴定与疾病相关的 DNA 多态性，我们研究了 176 名女性纤维肌痛患者的队列，并与 162 名健康女性的队列进行了比较。使用逻辑回归调整人群分层，研究了 48329 个标记物与纤维肌痛之间的关联。结果表明，有 29 个标记物的 P 值<1×10-5，最强的关联是 rs758459（P 值为 0.0001），位于基因中，该基因是 hsa-miR-130a-3p 的靶标。此外，变体 rs2295963 预测会影响 hsa-miR-1-3p 的结合。这两种 microRNA 之前在纤维肌痛患者中均有差异表达的报道。尽管其统计效力有限，但本研究报告了两个与 microRNA 相关的多态性，它们可能在纤维肌痛的发病机制中发挥功能作用。为了更好地理解疾病模式，需要对 microRNAs 和 microRNA 相关多态性的生物学意义进行进一步的功能分析。
