Identification of candidate genes associated with fibromyalgia susceptibility in southern Spanish women: the al-\xc1ndalus project

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

doi:10.1186/s12967-018-1416-8

Abstract

BackgroundCandidate-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.MethodsA 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.ResultsWe 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.ConclusionsWe 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.

Highlights

Candidate-gene studies on fibromyalgia susceptibility often include a small number of single nucleo‐ tide polymorphisms (SNPs), which is a limitation
The rs841and rs1799971 GG genotypes were more frequently observed in fibromyalgia than in controls [odds ratio (OR) (95% confidence interval, 95% CI) = 1.66 (1.03–2.67), p = 0.04 and 1.72 (1.11–2.67), p = 0.02, respectively; Table 1]
The rs2097903 AT/TT genotypes were present in the fibromyalgia participants more often than in their non-fibromyalgia peers [OR = 1.66 (1.02–2.71), p = 0.04; Table 1)

Summary

Introduction

Candidate-gene studies on fibromyalgia susceptibility often include a small number of single nucleo‐ tide polymorphisms (SNPs), which is a limitation. Fibromyalgia is a disease in which people experience chronic diffuse musculoskeletal pain that is usually accompanied by other symptoms such as fatigue, unrefreshed sleep, and cognitive problems [1,2,3,4]. This disease is nine times more common in women than in men [5]. Catechol-O-methyltransferase (COMT), the most widely studied gene in fibromyalgia, is involved in degrading catecholamines and several other neurotransmitters and, in modulating pain perception by the CNS. The association between COMT single nucleotide polymorphisms (SNPs) and fibromyalgia susceptibility is controversial [7, 8]

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Conclusion