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

ABSTRACT: 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.

SUBMITTER: Gloor Y

PROVIDER: S-EPMC9274135 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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

Gloor Yvonne Y Matthey Alain A Sobo Komla K Mouterde Médéric M Kosek Eva E Pickering Gisèle G Poloni Estella S ES Cedraschi Christine C Ehret Georg G Desmeules Jules A JA

Frontiers in neuroscience 20220628

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 usi ...[more]

PMID: 35837121

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Project description:BackgroundCentral sensitization (CS) is a condition characterized by a disproportionate response to pain stimuli, and is associated with chronic pain conditions such as fibromyalgia, but also with inflammatory arthropathies such as rheumatoid arthritis and psoriatic arthritis (PsA). CS has never been investigated in patients with psoriasis. The aim of this study is to investigate CS in patients with chronic plaque psoriasis.MethodsThis research involved a cross-sectional observational study of adult patients with moderate-to-severe psoriasis consecutively attending the outpatient clinic of the University Hospital of Verona. Demography, measures of disease severity or activity [i.e., Psoriasis Area and Severity Index (PASI), Disease Activity in Psoriatic Arthritis (DAPSA)], diagnosis of PsA, hypertension, and diabetes were collected. Central Sensitization Inventory (CSI), Dermatology Life Quality Index (DLQI), General Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) were administered.ResultsA total of 194 patients, including 115 (59%) men, with mean age of 54 ± 13 years, mean PASI of 12.7 ± 6.7, and mean DAPSA of 14.4 ± 3.8 were included. In total, 134 patients (79%) had only psoriasis while 60 (31%) had psoriasis and PsA; 19 (10%) patients had CSI score ≥ 40, which is the threshold for diagnosing CS. The proportion of CS ≥ 40 was higher in patients with PsA compared with psoriasis (17% versus 7%, p = 0.031). The mean CSI score in patients with PsA was higher compared with those with only psoriasis (27.5 ± 13.5 versus 20.7 ± 13.7, p = 0.002). An association between CSI and DLQI [β = 1.25 (95% CI 0.85-1.66)], PASI [β = 1.22 (95% CI 0.74-1.65)], GAD-7 [β = 2.07 (95% CI 1.69-2.45)] and PHQ-9 [β = 2.16 (95% CI 1.76-2.54)] was found independently from age, gender, diabetes, and PsA.ConclusionsCentral sensitization may be associated with psoriasis, particularly in those with high PASI, concomitant PsA, anxiety, depression, and severe quality of life impairment.

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Dataset Information

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

Publications

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

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