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Article

Association of Genetic Variants, Such as the μ-Opioid Receptor 1 (OPRM1) rs1799971 and Catechol-O-Methyltransferase (COMT) rs4680, with Phenotypic Expression of Fibromyalgia

by
Isabel Erenas Ondategui
1,
Julia Gómez Castro
2,
Sandra Estepa Hernández
3,
Celia Chicharro Miguel
3,4,
Regina Peiró Cárdenas
5,
Ana Fernández-Araque
2,6,7 and
Zoraida Verde
3,6,7,*
1
Faculty of Health Sciences, University of Valladolid, 42004 Soria, Spain
2
Department of Nursing, Faculty of Health Sciences, University of Valladolid, 42004 Soria, Spain
3
Department of Biochemistry, Molecular Biology and Physiology, Faculty of Health Sciences, University of Valladolid, 42004 Soria, Spain
4
Centro de Estudios Gregorio Marañón, Fundación Ortega-Marañón, 28010 Madrid, Spain
5
School of Medicine and Health Sciences, Tecnológico de Monterrey, Guadalajara 45201, Mexico
6
Grupo Investigación Reconocida (GIR) Farmacogenética, Genética del Cáncer, Polimorfismos Genéticos y Farmacoepidemiología, University of Valladolid, 47005 Valladolid, Spain
7
Unidad de Investigación Consolidada (UIC) de Castilla y León 387, University of Valladolid, 42004 Soria, Spain
*
Author to whom correspondence should be addressed.
Biomedicines 2025, 13(5), 1183; https://doi.org/10.3390/biomedicines13051183
Submission received: 2 April 2025 / Revised: 5 May 2025 / Accepted: 8 May 2025 / Published: 13 May 2025
(This article belongs to the Special Issue Advanced Research on Fibromyalgia (3rd Edition))
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Abstract

Background/Objectives: Genetic variants, such as the µ-opioid receptor 1 (OPRM1) rs1799971 and the catechol-O-methyltransferase (COMT) rs4680, have been considered among the potential causes in the development of some chronic pain conditions. In this regard, there are controversial results regarding their roles in fibromyalgia (FM). We aimed to investigate whether the OPRM1 rs1799971 and COMT rs4680 polymorphisms are associated with the development of or susceptibility to FM, as well as their potential association with syndrome characteristic variables, in a sample of the Spanish population with and without FM. Methods: The present study analysed COMT Val158Met and OPRM1 Asn40Asp genetic variants in 311 FM patients (301 women and 10 men) and 135 non-FM participants (120 women and 15 men). In addition to clinical variables, widespread pain index (WPI), symptom severity scale (SSS) (fatigue, rest quality, and cognitive symptoms), pain, stress episodes, and Borg scale were collected. Results: The main results indicate that women carrying the Val/Val genotype (i.e., high COMT activity) exhibited significantly lower levels of fatigue, cognitive impairment, and total SSS than heterozygote carriers. In addition, Met allele carriers (i.e., lower COMT activity) showed higher probabilities of suffering a stress episode and higher levels of exertion during daily activities. Conclusions: The present research suggests a link between dopaminergic dysfunction and exacerbated, frequently described symptoms in female FM patients. Although further research with wider genetic variants and recruited patients is needed, these results point out the necessity of considering gender as a separate category in chronic pain studies.
Keywords: genetic variants; fibromyalgia; COMT; OPRM1; fatigue; severity symptoms; borg scale; chronic pain; gender genetic variants; fibromyalgia; COMT; OPRM1; fatigue; severity symptoms; borg scale; chronic pain; gender
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MDPI and ACS Style

Erenas Ondategui, I.; Gómez Castro, J.; Estepa Hernández, S.; Chicharro Miguel, C.; Peiró Cárdenas, R.; Fernández-Araque, A.; Verde, Z. Association of Genetic Variants, Such as the μ-Opioid Receptor 1 (OPRM1) rs1799971 and Catechol-O-Methyltransferase (COMT) rs4680, with Phenotypic Expression of Fibromyalgia. Biomedicines 2025, 13, 1183. https://doi.org/10.3390/biomedicines13051183

AMA Style

Erenas Ondategui I, Gómez Castro J, Estepa Hernández S, Chicharro Miguel C, Peiró Cárdenas R, Fernández-Araque A, Verde Z. Association of Genetic Variants, Such as the μ-Opioid Receptor 1 (OPRM1) rs1799971 and Catechol-O-Methyltransferase (COMT) rs4680, with Phenotypic Expression of Fibromyalgia. Biomedicines. 2025; 13(5):1183. https://doi.org/10.3390/biomedicines13051183

Chicago/Turabian Style

Erenas Ondategui, Isabel, Julia Gómez Castro, Sandra Estepa Hernández, Celia Chicharro Miguel, Regina Peiró Cárdenas, Ana Fernández-Araque, and Zoraida Verde. 2025. "Association of Genetic Variants, Such as the μ-Opioid Receptor 1 (OPRM1) rs1799971 and Catechol-O-Methyltransferase (COMT) rs4680, with Phenotypic Expression of Fibromyalgia" Biomedicines 13, no. 5: 1183. https://doi.org/10.3390/biomedicines13051183

APA Style

Erenas Ondategui, I., Gómez Castro, J., Estepa Hernández, S., Chicharro Miguel, C., Peiró Cárdenas, R., Fernández-Araque, A., & Verde, Z. (2025). Association of Genetic Variants, Such as the μ-Opioid Receptor 1 (OPRM1) rs1799971 and Catechol-O-Methyltransferase (COMT) rs4680, with Phenotypic Expression of Fibromyalgia. Biomedicines, 13(5), 1183. https://doi.org/10.3390/biomedicines13051183

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