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

Fernando Estévez-López^{1

2}, Daniel Camiletti-Moirón³, Virginia A Aparicio⁴, Víctor Segura-Jiménez³, Inmaculada C Álvarez-Gallardo³, Alberto Soriano-Maldonado^{5

6}, Milkana Borges-Cosic⁷, Pedro Acosta-Manzano⁷, Rinie Geenen⁸, Manuel Delgado-Fernández⁷, Luis J Martínez-González⁹, Jonatan R Ruiz¹⁰, María J Álvarez-Cubero^{9

11}

Affiliations

¹ Department of Physical Education and Sport, Faculty of Sport Sciences, University of Granada, Carretera de Alfacar, s/n, 18011, Granada, Spain. festevez@ugr.es.
² Department of Psychology, Faculty of Social and Behavioural Sciences, Utrecht University, Utrecht, The Netherlands. festevez@ugr.es.
³ Department of Physical Education, Faculty of Education Sciences, University of Cádiz, Cádiz, Spain.
⁴ Department of Physiology, Faculty of Pharmacy, Faculty of Sport Sciences and Institute of Nutrition and Food Technology, University of Granada, Granada, Spain.
⁵ Department of Education, Faculty of Education Sciences, University of Almería, Almería, Spain.
⁶ SPORT Research Group (CTS-1024), CERNEP Research Center, University of Almería, Almería, Spain.
⁷ Department of Physical Education and Sport, Faculty of Sport Sciences, University of Granada, Carretera de Alfacar, s/n, 18011, Granada, Spain.
⁸ Department of Psychology, Faculty of Social and Behavioural Sciences, Utrecht University, Utrecht, The Netherlands.
⁹ Liquid Biopsy and Metastasis Research Group and Genomic Unit, GENyO (Pfizer-University of Granada, Andalusian Government Centre for Genomics and Oncological Research), Granada, Spain.
¹⁰ PROFITH "PROmoting FITness and Health Through Physical Activity" Research Group, Department of Physical Education and Sport, Faculty of Sport Sciences, University of Granada, Granada, Spain.
¹¹ Department of Biochemistry and Molecular Biology III, Faculty of Medicine, University of Granada, Granada, Spain.

PMID: 29486785
PMCID: PMC5828244
DOI: 10.1186/s12967-018-1416-8

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

Fernando Estévez-López et al. J Transl Med. 2018.

. 2018 Feb 27;16(1):43.

doi: 10.1186/s12967-018-1416-8.

Authors

Affiliations

¹ Department of Physical Education and Sport, Faculty of Sport Sciences, University of Granada, Carretera de Alfacar, s/n, 18011, Granada, Spain. festevez@ugr.es.
² Department of Psychology, Faculty of Social and Behavioural Sciences, Utrecht University, Utrecht, The Netherlands. festevez@ugr.es.
³ Department of Physical Education, Faculty of Education Sciences, University of Cádiz, Cádiz, Spain.
⁴ Department of Physiology, Faculty of Pharmacy, Faculty of Sport Sciences and Institute of Nutrition and Food Technology, University of Granada, Granada, Spain.
⁵ Department of Education, Faculty of Education Sciences, University of Almería, Almería, Spain.
⁶ SPORT Research Group (CTS-1024), CERNEP Research Center, University of Almería, Almería, Spain.
⁷ Department of Physical Education and Sport, Faculty of Sport Sciences, University of Granada, Carretera de Alfacar, s/n, 18011, Granada, Spain.
⁸ Department of Psychology, Faculty of Social and Behavioural Sciences, Utrecht University, Utrecht, The Netherlands.
⁹ Liquid Biopsy and Metastasis Research Group and Genomic Unit, GENyO (Pfizer-University of Granada, Andalusian Government Centre for Genomics and Oncological Research), Granada, Spain.
¹⁰ PROFITH "PROmoting FITness and Health Through Physical Activity" Research Group, Department of Physical Education and Sport, Faculty of Sport Sciences, University of Granada, Granada, Spain.
¹¹ Department of Biochemistry and Molecular Biology III, Faculty of Medicine, University of Granada, Granada, Spain.

PMID: 29486785
PMCID: PMC5828244
DOI: 10.1186/s12967-018-1416-8

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.

Keywords: Alleles; COMT gene; Caucasian; Chronic pain; Epidemiology; GCH1 gene; OPRM1 gene.

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References

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

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

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