ArticlePain2014
Epistasis between polymorphisms in COMT, ESR1, and GCH1 influences COMT enzyme activity and pain.
Article in Pain, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 77 citations in OpenAlex.
- The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions.Nature genetics · 2023Pooled it
- Pooled it
- Relationship Between Central Sensitization and Genetic Polymorphisms-A Case-Control Study in Fibromyalgia.European journal of pain (London, England) · 2026Trial
- Trial
- Vitamin D Receptor (VDR) Polymorphisms and Cardiometabolic Profiles in Orthopedic Patients: A Cluster-Based Analysis.International journal of molecular sciences · 2026Article
- Preclinical perspectives on disorders of the temporomandibular joint: Tracing the past, navigating the present, and shaping the future.The journal of pain · 2025Review
- Do Single-Nucleotide Polymorphisms Affect Pain Intensity and Sufentanil Analgesia After Pediatric Scoliosis Correction Surgery?International journal of molecular sciences · 2025Article
- A catechol-O-methyltransferase genetic variant impacts functional movement in tactical athletes.PloS one · 2025Article
- A mouse model of chronic primary pain that integrates clinically relevant genetic vulnerability, stress, and minor injury.Science translational medicine · 2024Article
- COMT and SCN9A gene variants do not contribute to chronic low back pain in Mexican-Mestizo patients.Acta neurochirurgica · 2024Article
- The incidence, impact, and risk factors for moderate to severe persistent pain after breast cancer surgery: a prospective cohort study.Pain medicine (Malden, Mass.) · 2023Article
- Transforming Growth Factor-β-Activated Kinase 1 (TAK1) Mediates Chronic Pain and Cytokine Production in Mouse Models of Inflammatory, Neuropathic, and Primary Pain.The journal of pain · 2023Article
- An Italian Twin Study of Non-Cancer Chronic Pain as a Wide Phenotype and Its Intensity.Medicina (Kaunas, Lithuania) · 2022Article
- Genetic and Clinical Factors Associated with Opioid Response in Chinese Han Patients with Cancer Pain: An Exploratory Cross-Sectional Study.Pain and therapy · 2022Article
- Painful Temporomandibular Joint Clicking: Genetic Point of View.Journal of oral & facial pain and headache · 2022Article
- Genetic and epigenetic mechanisms influencing acute to chronic postsurgical pain transitions in pediatrics: Preclinical to clinical evidence.Canadian journal of pain = Revue canadienne de la douleur · 2022Review
- Genetic variation in catechol-O-methyltransferase is associated with individual differences in conditioned pain modulation in healthy subjects.The journal of gene medicine · 2021Article
- Article
- Computational Functional Genomics-Based AmpliSeq™ Panel for Next-Generation Sequencing of Key Genes of Pain.International journal of molecular sciences · 2021Article
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
Abstract
Abnormalities in the enzymatic activity of catechol-O-methyltransferase (COMT) contribute to chronic pain conditions, such as temporomandibular disorders (TMD). Thus, we sought to determine the effects of polymorphisms in COMT and functionally related pain genes in the COMT pathway (estrogen receptor 1 [ESR1], guanosine-5-triphosphate cyclohydrolase 1 [GCH1], methylenetetrahydrofolate reductase [MTHFR]) on COMT enzymatic activity, musculoskeletal pain, and pain-related intermediate phenotypes among TMD cases and healthy control subjects. Results show that the COMT rs4680 (val(158)met) polymorphism is most strongly associated with outcome measures, such that individuals with the minor A allele (met) exhibit reduced COMT activity, increased TMD risk, and increased musculoskeletal pain. Epistatic interactions were observed between the COMT rs4680 polymorphism and polymorphisms in GCH1 and ESR1. Among individuals with the COMT met allele, those with 2 copies of the GCH1 rs10483639 minor G allele exhibit normalized COMT activity and increased mechanical pain thresholds. Among individuals with the COMT val allele, those with 2 copies of the ESR1 rs3020377 minor A allele exhibit reduced COMT activity, increased bodily pain, and poorer self-reported health. These data reveal that the GCH1 minor G allele confers a protective advantage among met carriers, whereas the ESR1 minor A allele is disadvantageous among val carriers. Furthermore, these data suggest that the ability to predict the downstream effects of genetic variation on COMT activity is critically important to understanding the molecular basis of chronic pain conditions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.