Uncovering a Genetic Polymorphism Located in Huntingtin Associated Protein 1 in Modulation of Central Pain Sensitization Signaling Pathways

Article Article scientifique Article Uncovering a Genetic Polymorphism Located in Huntingtin Associated Protein 1 in Modulation of Central Pain Sensitization Signaling Pathways eng 2022-06-28 2022-06-28 author Gloor Yvonne Sylvia 0000-0002-8790-0479 135176 author Matthey Alain 558446 author Sobo Komla 514524 author Mouterde Médéric 846036 author Kosek Eva author Pickering Gisèle author Poloni Estella S. 0000-0002-8465-003X 24418 author Cedraschi Christine 22343 author Ehret Georg Benedikt 98462 author Desmeules Jules Alexandre 73542 807773 10.3389/fnins.2022.807773 35837121 1662-453X PMC9274135 https://www.frontiersin.org/articles/10.3389/fnins.2022.807773/full <p> 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. </p> GWAS HAP1 Central sensitization Fibromyalgia Nociceptive flection reflex (NFR) threshold Dewey 616 Dewey 590 Dewey 617 Dewey 618 Swiss National Science Foundation Identification of genetic determinants for central pain sensitization in fibromyalgia patients 320030_182686 CH Project funding Swiss National Science Foundation Human genomic population structure and phenotype-genotype variation in ADME genes along a latitudinal transect from Africa to Europe 320030_159669 CH Project funding 44 Département de génétique et évolution 162 63 Département d'anesthésiologie, pharmacologie, soins intensifs et urgences 229 217 Centre de recherche clinique 201 56 Département de médecine 221 23 Institut de génétique et de génomique 0DH false 1247 Groupe Poloni 195 Aspects psychosociaux des maladies chroniques 247 302 Groupe Desmeules Jules (pharmacologie/toxicologie) 567 560 Génétique 901 682 Laboratory of Anthropology, Genetics and Peopling history (AGP) https://doi.org/10.26037/yareta:l35qwdy5t5b5vll3ae3hmzigy4 Frontiers in neuroscience 16 aa527c02-f9bb-41e7-b0c6-2021e1d1c3aa Article (Published version) Public Article-scientifique-from-unpaywall.pdf 1412483 application/pdf CC BY-4.0 5e486a38-72c7-4c58-9271-efb0a757004e Appendix Public PMC9274135_SupplementaryFiles.zip 2888302 application/zip openAccess Faculté des sciences / Section de biologie / Département de génétique et évolution Faculté de médecine / Section de médecine clinique / Département d'anesthésiologie, pharmacologie, soins intensifs et urgences Faculté de médecine / Centre de recherche clinique Faculté de médecine / Section de médecine clinique / Département de médecine Centres et instituts / Institut de génétique et de génomique

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Uncovering a Genetic Polymorphism Located in Huntingtin Associated Protein 1 in Modulation of Central Pain Sensitization Signaling Pathways	Frontiers in neuroscience	2022	380	64
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