Exploratory Analysis of Genetic Variants in BDNF, GABA Receptors, and Dopaminergic Pathways with Alcohol Use Disorder in a Spanish Cohort

Rojas-Pirela, Maura; Gómez Lesmes, Sandra Patricia; Salete-Granado, Daniel; Llorente, Hernán; Pérez Nieto, María-Ángeles; Novo-Veleiro, Ignacio; Cieza-Borrella, Clara; Pastor, Isabel; Fernández-Mateos, Javier; Inés Revuelta, Sandra M.; Chamorro, Antonio-Javier; Laso, Francisco-Javier; González-Sarmiento, Rogelio; Marcos, Miguel

doi:10.3390/ijms27125376

Open AccessArticle

Exploratory Analysis of Genetic Variants in BDNF, GABA Receptors, and Dopaminergic Pathways with Alcohol Use Disorder in a Spanish Cohort

by

Maura Rojas-Pirela

^1,2,3,†

,

Sandra Patricia Gómez Lesmes

^1,2,†,

Daniel Salete-Granado

^1,2,3

,

Hernán Llorente

⁴,

María-Ángeles Pérez Nieto

^2,3

,

Ignacio Novo-Veleiro

⁵,

Clara Cieza-Borrella

⁶

,

Isabel Pastor

^1,2,3,

Javier Fernández-Mateos

^1,2

,

Sandra M. Inés Revuelta

^1,2,3,

Antonio-Javier Chamorro

^1,2,3

,

Francisco-Javier Laso

^1,2,

Rogelio González-Sarmiento

^2,3

and

Miguel Marcos

^1,2,3,*

¹

Alcoholism Unit, Department of Internal Medicine, University Hospital of Salamanca, 37007 Salamanca, Spain

²

Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain

³

Department of Medicine, University of Salamanca, 37007 Salamanca, Spain

⁴

Department of Internal Medicine, Complejo Asistencial de Zamora, Salud Castilla y León, 49022 Zamora, Spain

⁵

Home Hospitalization and Palliative Care Service, Santiago de Compostela and Barbanza Health Area, 15706 Santiago de Compostela, Spain

⁶

Department of Molecular and Biomedical Sciences, School of Health and Medical Sciences, City St George’s, University of London, London SW17 0RE, UK

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2026, 27(12), 5376; https://doi.org/10.3390/ijms27125376

Submission received: 22 April 2026 / Revised: 8 June 2026 / Accepted: 11 June 2026 / Published: 15 June 2026

(This article belongs to the Section Molecular Neurobiology)

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Abstract

Alcohol use disorder (AUD) is influenced by genetic factors that affect key neurobiological systems, including dopaminergic and GABAergic pathways, which regulate neurobehavioral functions and are modulated by brain-derived neurotrophic factor (BDNF). Variations in these genes contribute to individual vulnerability to AUD. In this study, we investigated single-nucleotide polymorphisms (SNPs) and haplotypic associations in GABRA1, GABRA2, and GABRA6, along with the dopaminergic pathway genes DRD2/ANKK1 and BDNF, in a Spanish cohort. Peripheral blood-derived genomic DNA was genotyped, and haplotype analyses were conducted. Individual SNPs in GABRA1, GABRA2, BDNF, and DRD2/ANKK1 showed no significant associations with AUD. In GABRA6, the rs3219151 T allele was more frequent in AUD patients than in controls (57.9% vs. 49.3%; p = 0.03), while the C allele appeared to show a potential protective association. In addition, the GAC haplotype of GABRA6 (rs2197414, rs1992647, rs3219151) was less frequent in AUD than in controls (0.071 vs. 0.122) and showed a protective association (OR = 0.58; 95% CI = 0.34–0.99; p = 0.045). Our findings provide exploratory evidence suggesting that specific genetic variants and haplotypes may contribute to AUD susceptibility and support the relevance of multigenic and haplotypic approaches for exploring the neurobiological mechanisms underlying AUD.

Keywords: GABRA1; GABRA2; GABRA6; DRD2; ANKK1; BDNF; polymorphisms; genetic susceptibility

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MDPI and ACS Style

Rojas-Pirela, M.; Gómez Lesmes, S.P.; Salete-Granado, D.; Llorente, H.; Pérez Nieto, M.-Á.; Novo-Veleiro, I.; Cieza-Borrella, C.; Pastor, I.; Fernández-Mateos, J.; Inés Revuelta, S.M.; et al. Exploratory Analysis of Genetic Variants in BDNF, GABA Receptors, and Dopaminergic Pathways with Alcohol Use Disorder in a Spanish Cohort. Int. J. Mol. Sci. 2026, 27, 5376. https://doi.org/10.3390/ijms27125376

AMA Style

Rojas-Pirela M, Gómez Lesmes SP, Salete-Granado D, Llorente H, Pérez Nieto M-Á, Novo-Veleiro I, Cieza-Borrella C, Pastor I, Fernández-Mateos J, Inés Revuelta SM, et al. Exploratory Analysis of Genetic Variants in BDNF, GABA Receptors, and Dopaminergic Pathways with Alcohol Use Disorder in a Spanish Cohort. International Journal of Molecular Sciences. 2026; 27(12):5376. https://doi.org/10.3390/ijms27125376

Chicago/Turabian Style

Rojas-Pirela, Maura, Sandra Patricia Gómez Lesmes, Daniel Salete-Granado, Hernán Llorente, María-Ángeles Pérez Nieto, Ignacio Novo-Veleiro, Clara Cieza-Borrella, Isabel Pastor, Javier Fernández-Mateos, Sandra M. Inés Revuelta, and et al. 2026. "Exploratory Analysis of Genetic Variants in BDNF, GABA Receptors, and Dopaminergic Pathways with Alcohol Use Disorder in a Spanish Cohort" International Journal of Molecular Sciences 27, no. 12: 5376. https://doi.org/10.3390/ijms27125376

APA Style

Rojas-Pirela, M., Gómez Lesmes, S. P., Salete-Granado, D., Llorente, H., Pérez Nieto, M.-Á., Novo-Veleiro, I., Cieza-Borrella, C., Pastor, I., Fernández-Mateos, J., Inés Revuelta, S. M., Chamorro, A.-J., Laso, F.-J., González-Sarmiento, R., & Marcos, M. (2026). Exploratory Analysis of Genetic Variants in BDNF, GABA Receptors, and Dopaminergic Pathways with Alcohol Use Disorder in a Spanish Cohort. International Journal of Molecular Sciences, 27(12), 5376. https://doi.org/10.3390/ijms27125376

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Exploratory Analysis of Genetic Variants in BDNF, GABA Receptors, and Dopaminergic Pathways with Alcohol Use Disorder in a Spanish Cohort

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