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A genetic polymorphism that is associated with mitochondrial energy metabolism increases risk of fibromyalgia.

Publication ,  Journal Article
van Tilburg, MAL; Parisien, M; Boles, RG; Drury, GL; Smith-Voudouris, J; Verma, V; Khoury, S; Chabot-Doré, A-J; Nackley, AG; Smith, SB ...
Published in: Pain
December 2020

Alterations in cellular energy metabolism have been implicated in chronic pain, suggesting a role for mitochondrial DNA. Previous studies reported associations of a limited number of mitochondrial DNA polymorphisms with specific pain conditions. In this study, we examined the full mitochondrial genomes of people with a variety of chronic pain conditions. A discovery cohort consisting of 609 participants either with or without a complex persistent pain conditions (CPPCs) was examined. Mitochondrial DNA was subjected to deep sequencing for identification of rare mutations, common variants, haplogroups, and heteroplasmy associated with 5 CPPCs: episodic migraine, irritable bowel syndrome, fibromyalgia, vulvar vestibulitis, or temporomandibular disorders. The strongest association found was the presence of the C allele at the single nucleotide polymorphism m.2352T>C (rs28358579) that significantly increased the risk for fibromyalgia (odds ratio [OR] = 4.6, P = 4.3 × 10). This relationship was even stronger in women (OR = 5.1, P = 2.8 × 10), and m.2352T>C was associated with all other CPPCs in a consistent risk-increasing fashion. This finding was replicated in another cohort (OR = 4.3, P = 2.6 × 10) of the Orofacial Pain: Prospective Evaluation and Risk Assessment study consisting of 1754 female participants. To gain insight into the cellular consequences of the associated genetic variability, we conducted an assay testing metabolic reprogramming in human cell lines with defined genotypes. The minor allele C was associated with decreased mitochondrial membrane potential under conditions where oxidative phosphorylation is required, indicating a role of oxidative phosphorylation in pathophysiology of chronic pain. Our results suggest that cellular energy metabolism, modulated by m.2352T>C, contributes to fibromyalgia and possibly other chronic pain conditions.

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Published In

Pain

DOI

EISSN

1872-6623

Publication Date

December 2020

Volume

161

Issue

12

Start / End Page

2860 / 2871

Location

United States

Related Subject Headings

  • Prospective Studies
  • Mitochondria
  • Humans
  • Fibromyalgia
  • Female
  • Energy Metabolism
  • Chronic Pain
  • Anesthesiology
  • 52 Psychology
  • 42 Health sciences
 

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ICMJE
MLA
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van Tilburg, M. A. L., Parisien, M., Boles, R. G., Drury, G. L., Smith-Voudouris, J., Verma, V., … Diatchenko, L. (2020). A genetic polymorphism that is associated with mitochondrial energy metabolism increases risk of fibromyalgia. Pain, 161(12), 2860–2871. https://doi.org/10.1097/j.pain.0000000000001996
Tilburg, Miranda A. L. van, Marc Parisien, Richard G. Boles, Gillian L. Drury, Julian Smith-Voudouris, Vivek Verma, Samar Khoury, et al. “A genetic polymorphism that is associated with mitochondrial energy metabolism increases risk of fibromyalgia.Pain 161, no. 12 (December 2020): 2860–71. https://doi.org/10.1097/j.pain.0000000000001996.
van Tilburg MAL, Parisien M, Boles RG, Drury GL, Smith-Voudouris J, Verma V, et al. A genetic polymorphism that is associated with mitochondrial energy metabolism increases risk of fibromyalgia. Pain. 2020 Dec;161(12):2860–71.
van Tilburg, Miranda A. L., et al. “A genetic polymorphism that is associated with mitochondrial energy metabolism increases risk of fibromyalgia.Pain, vol. 161, no. 12, Dec. 2020, pp. 2860–71. Pubmed, doi:10.1097/j.pain.0000000000001996.
van Tilburg MAL, Parisien M, Boles RG, Drury GL, Smith-Voudouris J, Verma V, Khoury S, Chabot-Doré A-J, Nackley AG, Smith SB, Whitehead WE, Zolnoun DA, Slade GD, Tchivileva I, Maixner W, Diatchenko L. A genetic polymorphism that is associated with mitochondrial energy metabolism increases risk of fibromyalgia. Pain. 2020 Dec;161(12):2860–2871.

Published In

Pain

DOI

EISSN

1872-6623

Publication Date

December 2020

Volume

161

Issue

12

Start / End Page

2860 / 2871

Location

United States

Related Subject Headings

  • Prospective Studies
  • Mitochondria
  • Humans
  • Fibromyalgia
  • Female
  • Energy Metabolism
  • Chronic Pain
  • Anesthesiology
  • 52 Psychology
  • 42 Health sciences