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A family-based study to identify genetic biomarkers of fibromyalgia: consideration of patients’ subgroups
M.C. Gerra1, A. González-Villar2, L. Arendt-Nielsen3, I. Søkilde Pedersen4, Y. Triñanes5, C. Donnini6, M. Manfredini7, D. Walther8, G.L. Moeller9, M. Pidal-Miranda10, S. Romero-Yuste11, M. Arias-Gómez12, M.T. Carrillo-De-La-Peña13
- Centre for Neuroplasticity and Pain (CNAP), SMI®, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark. mcg@hst.aau.dk
- Department of Clinical Psychology and Psychobiology, University of Santiago de Compostela, Spain.
- Centre for Neuroplasticity and Pain (CNAP), SMI®, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
- Aalborg University Hospital and Aalborg University, Molecular Diagnostics and Department of Clinical Medicine, Aalborg, Denmark.
- Department of Clinical Psychology and Psychobiology, University of Santiago de Compostela, Spain.
- Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parma, Italy.
- Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parma, Italy.
- Designer Drug Research Unit, Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
- Genokey ApS, ScionDTU, Technical University of Denmark, Hoersholm, Denmark.
- Department of Clinical Psychology and Psychobiology, University of Santiago de Compostela, Spain.
- Rheumatology Service, University Complex Hospital of Pontevedra, Spain.
- Neurology Service, University Complex Hospital of Santiago de Compostela, Spain.
- Department of Clinical Psychology and Psychobiology, University of Santiago de Compostela, Spain.
CER14700
2021 Vol.39, N°3 ,Suppl.130
PI 0144, PF 0152
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PMID: 34161225 [PubMed]
Received: 07/04/2021
Accepted : 20/05/2021
In Press: 10/06/2021
Published: 21/06/2021
Abstract
OBJECTIVES:
Evidence from genome-wide and candidate gene association studies, familial aggregation and linkage analyses demonstrate the genetic contribution to fibromyalgia (FM) disease. This study aimed to identify genetic biomarkers of FM and its related comorbid disorders, by exploring 41 polymorphisms potentially involved in FM pathogenesis in families with at least one patient with FM.
METHODS:
Core symptoms were assessed, and blood samples collected from 556 patients with FM and 395 healthy relatives. For the genetic study, a final sample of 401 FM patients and 232 healthy controls was selected, discarding patients with concomitant pathologies and controls with chronic pain. A family-based approach using DFAM test (Plink) and SNPs (single nucleotide polymorphisms) combination analyses to compare FM patients vs. controls were first applied. Second, the genotypic distribution of subgroups of FM patients, stratified by severe vs. mild symptoms of pain, depression and sleep impairment, was considered.
RESULTS:
No evidence of associations with FM per se were detected, using either a family-based approach or SNPs combination analyses. However, considering the subgroups of FM patients, the SNP rs6454674 (CNR1, cannabinoid receptor 1 gene) was found as a potential genetic marker of FM correlated with depression (p<.001).
CONCLUSIONS:
No significant associations using either the family-based analysis or the SNPs combination tests dissociated FM patients and their healthy relatives. FM patients with and without depression showed a significant difference in the genotypic distribution related to the SNP rs6454674 in the cannabinoid receptor 1 gene (CNR1) indicating that FM is not a homogenous disorder.