Identification of potential mechanism and hub genes for neuropathic pain by expression‐based genome‐wide association study

Gu, Yu; Qiu, Zhuolin; Cheng, Nan; Chen, Chaojin; Hei, Ziqing; Li, Xiang

doi:10.1002/jcb.27766

Cited by 9 publications

(7 citation statements)

References 39 publications

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“…Quantitative real‐time polymerase chain reaction (qRT-PCR) was conducted as reported previously [15]. In short, total RNA was extracted from snap-frozen DRG and spinal cord tissues using TRIzol reagent (Thermo Fisher Scientific, Waltham, MA, U.S.A.).…”

Section: Methodsmentioning

confidence: 99%

“…Western blotting was performed following the standard procedures as previously described [15] by using the following antibodies: C–C motif chemokine ligand 2 (CCL2) (rabbit, 1:1000, Novus, Littleton, CO); allograft inflammatory factor 1 (AIF1; rabbit, 1:1000, Novus); tissue inhibitor of metalloproteinase 1 (TIMP1) (rabbit, 1:1000, Sigma–Aldrich, St. Louis, MO) and β-actin (1:3000; Sigma–Aldrich). All Western blots were repeated at least three times.…”

Section: Methodsmentioning

confidence: 99%

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Weighted gene co-expression network analysis reveals specific modules and hub genes related to neuropathic pain in dorsal root ganglions

Cheng

Zhang

Guo³

et al. 2019

Bioscience Reports

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Neuropathic pain is a common, debilitating clinical issue. Here, the weighted gene co-expression network analysis (WGCNA) was used to identify the specific modules and hub genes that are related to neuropathic pain. The microarray dataset of a neuropathic rat model induced by tibial nerve transection (TNT), including dorsal root ganglion (DRG) tissues from TNT model (n=7) and sham (n=8) rats, was downloaded from the ArrayExpress database (E-MTAB-2260). The co-expression network modules were identified by the WGCNA package. The protein–protein interaction (PPI) network was constructed, and the node with highest level of connectivity in the network were identified as the hub gene. A total of 1739 genes and seven modules were identified. The most significant module was the brown module, which contained 215 genes that were primarily associated with the biological process (BP) of the defense response and molecular function of calcium ion binding. Furthermore, C–C motif chemokine ligand 2 (Ccl2), Fos and tissue inhibitor of metalloproteinase 1 (Timp1) which were identified as the hub genes in the PPI network and two subnetworks separately. The in vivo studies validated that mRNA and protein levels of Ccl2, Fos and Timp1 were up-regulated in DRG and spinal cord tissues after TNT. The present study offers novel insights into the molecular mechanisms of neuropathic pain in the context of peripheral nerve injury.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Weighted gene co-expression network analysis reveals specific modules and hub genes related to neuropathic pain in dorsal root ganglions

Cheng

Zhang

Guo³

et al. 2019

Bioscience Reports

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“…Several candidate loci were reported to be associated with pain conditions, including diabetic neuropathic pain. 29 – 32 …”

Section: Introductionmentioning

confidence: 99%

Genome-wide association study identifies candidate loci associated with chronic pain and postherpetic neuralgia

et al. 2021

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Background Human twin studies and other studies have indicated that chronic pain has heritability that ranges from 30% to 70%. We aimed to identify potential genetic variants that contribute to the susceptibility to chronic pain and efficacy of administered drugs. We conducted genome-wide association studies (GWASs) using whole-genome genotyping arrays with more than 700,000 markers in 191 chronic pain patients and a subgroup of 89 patients with postherpetic neuralgia (PHN) in addition to 282 healthy control subjects in several genetic models, followed by additional gene-based and gene-set analyses of the same phenotypes. We also performed a GWAS for the efficacy of drugs for the treatment of pain. Results Although none of the single-nucleotide polymorphisms (SNPs) were found to be genome-wide significantly associated with chronic pain ( p ≥ 1.858 × 10−7), the GWAS of PHN patients revealed that the rs4773840 SNP within the ABCC4 gene region was significantly associated with PHN in the trend model (nominal p = 1.638 × 10−7). In the additional gene-based analysis, one gene, PRKCQ, was significantly associated with chronic pain in the trend model (adjusted p = 0.03722). In the gene-set analysis, several gene sets were significantly associated with chronic pain and PHN. No SNPs were significantly associated with the efficacy of any of types of drugs in any of the genetic models. Conclusions These results suggest that the PRKCQ gene and rs4773840 SNP within the ABCC4 gene region may be related to the susceptibility to chronic pain conditions and PHN, respectively.

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“…GO and KEGG enrichment analyses uncovered that these functions were associated with the occurrence and development of NP. Additionally, complement and coagulation cascade [ 30 ], neuroactive ligand-receptor [ 31 ], and ECM-receptor interactions [ 32 ] were signaling pathways related to various functions mediated by NP. The genes associated with these pathways were also observed in our analysis.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Potential Hub Genes for Neuropathic Pain Based on Differential Expression in Rat Models

Bai

Geng

Wang

et al. 2022

Pain Research and Management

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Objective. Neuropathic pain (NP) is a type of intractable chronic pain with complicated etiology. The exact molecular mechanism underlying NP remains unclear. In this study, we searched for molecular biomarkers of NP. Methods. Differentially expressed genes (DEGs) were predicted by analyzing three NP-related microarray datasets in Gene Expression Omnibus with robust rank aggregation. A weighted gene coexpression network analysis was conducted to construct a network of differentially expressed genes, followed by the evaluation of correlations between gene sets and the determination of hub genes. The candidate genes from the key module were identified using a gene set enrichment analysis. Results. In total, 353 upregulated and 383 downregulated genes were obtained, among which five hub genes were determined to be related to pain phenotypes. Reverse transcription-quantitative polymerase chain reaction was performed to verify the expression of these hub genes in the dorsal root ganglia of rats with spared nerve injury, which revealed the decreased expression of EMC4. Hence, EMC4 was defined as a biomarker for NP development. Conclusions. The results of this study form a basis for further research into the mechanism of NP development and are expected to aid in the development of novel therapeutic strategies.

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Identification of potential mechanism and hub genes for neuropathic pain by expression‐based genome‐wide association study

Cited by 9 publications

References 39 publications

Weighted gene co-expression network analysis reveals specific modules and hub genes related to neuropathic pain in dorsal root ganglions

Weighted gene co-expression network analysis reveals specific modules and hub genes related to neuropathic pain in dorsal root ganglions

Genome-wide association study identifies candidate loci associated with chronic pain and postherpetic neuralgia

Analysis of Potential Hub Genes for Neuropathic Pain Based on Differential Expression in Rat Models

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