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Published in: Journal of Translational Medicine 1/2018

Open Access 01-12-2018 | Research

Identification of candidate genes associated with fibromyalgia susceptibility in southern Spanish women: the al-Ándalus project

Authors: Fernando Estévez-López, Daniel Camiletti-Moirón, Virginia A. Aparicio, Víctor Segura-Jiménez, Inmaculada C. Álvarez-Gallardo, Alberto Soriano-Maldonado, Milkana Borges-Cosic, Pedro Acosta-Manzano, Rinie Geenen, Manuel Delgado-Fernández, Luis J. Martínez-González, Jonatan R. Ruiz, María J. Álvarez-Cubero

Published in: Journal of Translational Medicine | Issue 1/2018

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Abstract

Background

Candidate-gene studies on fibromyalgia susceptibility often include a small number of single nucleotide polymorphisms (SNPs), which is a limitation. Moreover, there is a paucity of evidence in Europe. Therefore, we compared genotype frequencies of candidate SNPs in a well-characterised sample of Spanish women with fibromyalgia and healthy non-fibromyalgia women.

Methods

A total of 314 women with a diagnosis of fibromyalgia (cases) and 112 non-fibromyalgia healthy (controls) women participated in this candidate-gene study. Buccal swabs were collected for DNA extraction. Using TaqMan™ OpenArray™, we analysed 61 SNPs of 33 genes related to fibromyalgia susceptibility, symptoms, or potential mechanisms.

Results

We observed that the rs841 and rs1799971 GG genotype was more frequently observed in fibromyalgia than in controls (p = 0.04 and p = 0.02, respectively). The rs2097903 AT/TT genotypes were also more often present in the fibromyalgia participants than in their control peers (p = 0.04). There were no differences for the remaining SNPs.

Conclusions

We identified, for the first time, associations of the rs841 (guanosine triphosphate cyclohydrolase 1 gene) and rs2097903 (catechol-O-methyltransferase gene) SNPs with higher risk of fibromyalgia susceptibility. We also confirmed that the rs1799971 SNP (opioid receptor μ1 gene) might confer genetic risk of fibromyalgia. We did not adjust for multiple comparisons, which would be too stringent and yield to non-significant differences in the genotype frequencies between cases and controls. Our findings may be biologically meaningful and informative, and should be further investigated in other populations. Of particular interest is to replicate the present study in a larger independent sample to confirm or refute our findings. On the other hand, by including 61 SNPs of 33 candidate-genes with a strong rationale (they were previously investigated in relation to fibromyalgia susceptibility, symptoms or potential mechanisms), the present research is the most comprehensive candidate-gene study on fibromyalgia susceptibility to date.
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Literature
1.
go back to reference Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. 1990; 33:160–72. http://www.ncbi.nlm.nih.gov/pubmed/2306288. Accessed 18 Jan 2015. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. 1990; 33:160–72. http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​2306288. Accessed 18 Jan 2015.
2.
go back to reference Wolfe F, Clauw DJ, Fitzcharles M-A, Goldenberg DL, Häuser W, Katz RS, et al. Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia. J Rheumatol. 2011;38:1113–22.CrossRefPubMed Wolfe F, Clauw DJ, Fitzcharles M-A, Goldenberg DL, Häuser W, Katz RS, et al. Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia. J Rheumatol. 2011;38:1113–22.CrossRefPubMed
3.
go back to reference Wolfe F, Clauw DJ, Fitzcharles M-A, Goldenberg DL, Häuser W, Katz RL, et al. 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum. 2016;46:319–29.CrossRefPubMed Wolfe F, Clauw DJ, Fitzcharles M-A, Goldenberg DL, Häuser W, Katz RL, et al. 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum. 2016;46:319–29.CrossRefPubMed
8.
go back to reference Vargas-Alarcón G, Fragoso J-M, Cruz-Robles D, Vargas A, Vargas A, Lao-Villadóniga J-I, et al. Catechol-O-methyltransferase gene haplotypes in Mexican and Spanish patients with fibromyalgia. Arthritis Res Ther. 2007;9:R110.CrossRefPubMedPubMedCentral Vargas-Alarcón G, Fragoso J-M, Cruz-Robles D, Vargas A, Vargas A, Lao-Villadóniga J-I, et al. Catechol-O-methyltransferase gene haplotypes in Mexican and Spanish patients with fibromyalgia. Arthritis Res Ther. 2007;9:R110.CrossRefPubMedPubMedCentral
9.
go back to reference Kim SK, Kim SH, Nah SS, Hyun Lee J, Hong SJ, Kim HS, et al. Association of guanosine triphosphate cyclohydrolase 1 gene polymorphisms with fibromyalgia syndrome in a Korean population. J Rheumatol. 2013;40:316–22.CrossRefPubMed Kim SK, Kim SH, Nah SS, Hyun Lee J, Hong SJ, Kim HS, et al. Association of guanosine triphosphate cyclohydrolase 1 gene polymorphisms with fibromyalgia syndrome in a Korean population. J Rheumatol. 2013;40:316–22.CrossRefPubMed
10.
go back to reference Solak Ö, Erdoǧan MÖ, Yildiz H, Ulaşli AM, Yaman F, Terzi ESA, et al. Assessment of opioid receptor μ1 gene A118G polymorphism and its association with pain intensity in patients with fibromyalgia. Rheumatol Int. 2014;34(9):1257–61.CrossRefPubMed Solak Ö, Erdoǧan MÖ, Yildiz H, Ulaşli AM, Yaman F, Terzi ESA, et al. Assessment of opioid receptor μ1 gene A118G polymorphism and its association with pain intensity in patients with fibromyalgia. Rheumatol Int. 2014;34(9):1257–61.CrossRefPubMed
11.
go back to reference Estévez-López F, Aparicio VA, Ruiz JR, Martínez-González LJ, Delgado-Fernández M, Álvarez-Cubero MJ. The TT genotype of the rs6860 polymorphism of the charged multivesicular body protein 1A gene is associated with susceptibility to fibromyalgia in southern Spanish women. Rheumatol Int. 2017;15:1–3. http://www.ncbi.nlm.nih.gov/pubmed/29247346. Estévez-López F, Aparicio VA, Ruiz JR, Martínez-González LJ, Delgado-Fernández M, Álvarez-Cubero MJ. The TT genotype of the rs6860 polymorphism of the charged multivesicular body protein 1A gene is associated with susceptibility to fibromyalgia in southern Spanish women. Rheumatol Int. 2017;15:1–3. http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​29247346.
14.
15.
19.
go back to reference Estévez-López F, Segura-Jiménez V, Álvarez-Gallardo ICIC, Borges-Cosic M, Pulido-Martos M, Carbonell-Baeza A, et al. Adaptation profiles comprising objective and subjective measures in fibromyalgia: the al-Ándalus project. Rheumatology (Oxford). 2017;56:2015–24. http://www.ncbi.nlm.nih.gov/pubmed/28968914. Estévez-López F, Segura-Jiménez V, Álvarez-Gallardo ICIC, Borges-Cosic M, Pulido-Martos M, Carbonell-Baeza A, et al. Adaptation profiles comprising objective and subjective measures in fibromyalgia: the al-Ándalus project. Rheumatology (Oxford). 2017;56:2015–24. http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​28968914.
20.
go back to reference Segura-Jiménez V, Soriano-Maldonado A, Estévez-López F, Álvarez-Gallardo ICIC, Delgado-Fernández M, Ruiz JRJR, et al. Independent and joint associations of physical activity and fitness with fibromyalgia symptoms and severity: The al-Ándalus project. J Sports Sci. 2017;35:1565–74. http://www.ncbi.nlm.nih.gov/pubmed/27618648. Accessed 30 Nov 2016. Segura-Jiménez V, Soriano-Maldonado A, Estévez-López F, Álvarez-Gallardo ICIC, Delgado-Fernández M, Ruiz JRJR, et al. Independent and joint associations of physical activity and fitness with fibromyalgia symptoms and severity: The al-Ándalus project. J Sports Sci. 2017;35:1565–74. http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​27618648. Accessed 30 Nov 2016.
25.
go back to reference Vargas-Alarcón G, Fragoso JM, Cruz-Robles D, Vargas A, Martinez A, Lao-Villadóniga JI, et al. Association of adrenergic receptor gene polymorphisms with different fibromyalgia syndrome domains. Arthritis Rheum. 2009;60:2169–73.CrossRefPubMed Vargas-Alarcón G, Fragoso JM, Cruz-Robles D, Vargas A, Martinez A, Lao-Villadóniga JI, et al. Association of adrenergic receptor gene polymorphisms with different fibromyalgia syndrome domains. Arthritis Rheum. 2009;60:2169–73.CrossRefPubMed
Metadata
Title
Identification of candidate genes associated with fibromyalgia susceptibility in southern Spanish women: the al-Ándalus project
Authors
Fernando Estévez-López
Daniel Camiletti-Moirón
Virginia A. Aparicio
Víctor Segura-Jiménez
Inmaculada C. Álvarez-Gallardo
Alberto Soriano-Maldonado
Milkana Borges-Cosic
Pedro Acosta-Manzano
Rinie Geenen
Manuel Delgado-Fernández
Luis J. Martínez-González
Jonatan R. Ruiz
María J. Álvarez-Cubero
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2018
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-018-1416-8

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