Uncovering a Genetic Polymorphism Located in Huntingtin Associated Protein 1 in Modulation of Central Pain Sensitization Signaling Pathways
Fibromyalgia syndrome (FMS) is characterized by widespread pain and increased sensitivity to nociceptive stimulus or tenderness. While familial aggregation could suggest a potential hereditary component in FMS development, isolation of genetic determinants has proven difficult due to the multi-facto...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2022.807773/full |
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| author | Yvonne Gloor Alain Matthey Komla Sobo Médéric Mouterde Eva Kosek Gisèle Pickering Gisèle Pickering Estella S. Poloni Estella S. Poloni Christine Cedraschi Georg Ehret Jules A. Desmeules Jules A. Desmeules |
| author_facet | Yvonne Gloor Alain Matthey Komla Sobo Médéric Mouterde Eva Kosek Gisèle Pickering Gisèle Pickering Estella S. Poloni Estella S. Poloni Christine Cedraschi Georg Ehret Jules A. Desmeules Jules A. Desmeules |
| author_sort | Yvonne Gloor |
| collection | DOAJ |
| description | Fibromyalgia syndrome (FMS) is characterized by widespread pain and increased sensitivity to nociceptive stimulus or tenderness. While familial aggregation could suggest a potential hereditary component in FMS development, isolation of genetic determinants has proven difficult due to the multi-factorial nature and complexity of the syndrome. Central sensitization is thought to be one of the key mechanisms leading to FMS in a subset of patients. Enhanced central pain signaling can be measured using the Nociceptive Flexion Reflex (NFR) or RIII threshold. We performed a genome-wide association study (GWAS) using an array to genotype 258,756 human genetic polymorphisms in 225 FMS patients and 77 healthy volunteers and searched for genetic variants associated with a lowered NFR threshold. We have identified a potential association between a single nucleotide polymorphism resulting in a common non-synonymous coding mutation in the Huntingtin associated protein 1 (HAP1) gene (rs4796604, MAF = 0.5) and the NFR threshold (p = 4.78E−06). The Hap1 protein is involved in trafficking and is particularly enriched in neurons. Our results suggest a possible involvement of the neuronal trafficking protein HAP1 in modulating pain signaling pathways and thus participate in the establishment of the NFR threshold. |
| first_indexed | 2024-12-12T14:15:56Z |
| format | Article |
| id | doaj.art-f6d85e8d71574aa9b0e5e62a99d4046e |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-12T14:15:56Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-f6d85e8d71574aa9b0e5e62a99d4046e2022-12-22T00:21:54ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-06-011610.3389/fnins.2022.807773807773Uncovering a Genetic Polymorphism Located in Huntingtin Associated Protein 1 in Modulation of Central Pain Sensitization Signaling PathwaysYvonne Gloor0Alain Matthey1Komla Sobo2Médéric Mouterde3Eva Kosek4Gisèle Pickering5Gisèle Pickering6Estella S. Poloni7Estella S. Poloni8Christine Cedraschi9Georg Ehret10Jules A. Desmeules11Jules A. Desmeules12Division of Clinical Pharmacology and Toxicology, Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals (HUG), Geneva, SwitzerlandClinical Investigation Unit, Clinical Research Center (CRC), Geneva University Hospitals (HUG), Geneva, SwitzerlandDivision of Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospitals (HUG), Geneva, SwitzerlandAnthropology Unit, Department of Genetics and Evolution, University of Geneva, Geneva, SwitzerlandDepartment of Clinical Neurosciences, Karolinska Institutet, Stockholm, SwedenClinical Investigation Center, Inserm 1405, Centre Hospitalier Universitaire, Clermont-Ferrand, FranceClinical Investigation Center, Inserm 1405, University Hospital, Clermont-Ferrand, FranceAnthropology Unit, Department of Genetics and Evolution, University of Geneva, Geneva, SwitzerlandInstitute of Genetics and Genomics of Geneva (iGE3), Geneva, SwitzerlandDivision of Clinical Pharmacology and Toxicology, Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals (HUG), Geneva, SwitzerlandDivision of Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospitals (HUG), Geneva, SwitzerlandDivision of Clinical Pharmacology and Toxicology, Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals (HUG), Geneva, SwitzerlandClinical Investigation Unit, Clinical Research Center (CRC), Geneva University Hospitals (HUG), Geneva, SwitzerlandFibromyalgia syndrome (FMS) is characterized by widespread pain and increased sensitivity to nociceptive stimulus or tenderness. While familial aggregation could suggest a potential hereditary component in FMS development, isolation of genetic determinants has proven difficult due to the multi-factorial nature and complexity of the syndrome. Central sensitization is thought to be one of the key mechanisms leading to FMS in a subset of patients. Enhanced central pain signaling can be measured using the Nociceptive Flexion Reflex (NFR) or RIII threshold. We performed a genome-wide association study (GWAS) using an array to genotype 258,756 human genetic polymorphisms in 225 FMS patients and 77 healthy volunteers and searched for genetic variants associated with a lowered NFR threshold. We have identified a potential association between a single nucleotide polymorphism resulting in a common non-synonymous coding mutation in the Huntingtin associated protein 1 (HAP1) gene (rs4796604, MAF = 0.5) and the NFR threshold (p = 4.78E−06). The Hap1 protein is involved in trafficking and is particularly enriched in neurons. Our results suggest a possible involvement of the neuronal trafficking protein HAP1 in modulating pain signaling pathways and thus participate in the establishment of the NFR threshold.https://www.frontiersin.org/articles/10.3389/fnins.2022.807773/fullcentral sensitizationnociceptive flection reflex (NFR) thresholdfibromyalgiaGWASHAP1 |
| spellingShingle | Yvonne Gloor Alain Matthey Komla Sobo Médéric Mouterde Eva Kosek Gisèle Pickering Gisèle Pickering Estella S. Poloni Estella S. Poloni Christine Cedraschi Georg Ehret Jules A. Desmeules Jules A. Desmeules Uncovering a Genetic Polymorphism Located in Huntingtin Associated Protein 1 in Modulation of Central Pain Sensitization Signaling Pathways Frontiers in Neuroscience central sensitization nociceptive flection reflex (NFR) threshold fibromyalgia GWAS HAP1 |
| title | Uncovering a Genetic Polymorphism Located in Huntingtin Associated Protein 1 in Modulation of Central Pain Sensitization Signaling Pathways |
| title_full | Uncovering a Genetic Polymorphism Located in Huntingtin Associated Protein 1 in Modulation of Central Pain Sensitization Signaling Pathways |
| title_fullStr | Uncovering a Genetic Polymorphism Located in Huntingtin Associated Protein 1 in Modulation of Central Pain Sensitization Signaling Pathways |
| title_full_unstemmed | Uncovering a Genetic Polymorphism Located in Huntingtin Associated Protein 1 in Modulation of Central Pain Sensitization Signaling Pathways |
| title_short | Uncovering a Genetic Polymorphism Located in Huntingtin Associated Protein 1 in Modulation of Central Pain Sensitization Signaling Pathways |
| title_sort | uncovering a genetic polymorphism located in huntingtin associated protein 1 in modulation of central pain sensitization signaling pathways |
| topic | central sensitization nociceptive flection reflex (NFR) threshold fibromyalgia GWAS HAP1 |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2022.807773/full |
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