AUTHOR=Gloor Yvonne , Matthey Alain , Sobo Komla , Mouterde Médéric , Kosek Eva , Pickering Gisèle , Poloni Estella S. , Cedraschi Christine , Ehret Georg , Desmeules Jules A. 

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

JOURNAL=Frontiers in Neuroscience

VOLUME=16

YEAR=2022

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.807773

DOI=10.3389/fnins.2022.807773

ISSN=1662-453X

ABSTRACT=<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 (<italic>HAP1</italic>) gene (rs4796604, MAF = 0.5) and the NFR threshold (<italic>p</italic> = 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>