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Impact of genetic variations in ADORA2A gene on depression and symptoms: a cross-sectional population-based study

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Abstract

Genetic variants involved in adenosine metabolism and its receptors were associated with increased risk for psychiatric disorders, including anxiety, depression, and schizophrenia. Here, we examined an association between a single nucleotide polymorphism in A2A receptor gene (ADORA2A, rs2298383 SNP) with current depressive episode and symptom profile. A total of 1253 individuals from a cross-sectional population-based study were analyzed by the Mini International Neuropsychiatric Interview 5.0. Our data showed that the TT genotype of ADORA2A rs2298383 SNP was associated with reduced risk for depression when compared to the CC/CT genotypes (p = 0.020). This association remained significant after adjusting for confounding variables such as smoking, gender, socioeconomic class, and ethnicity (OR = 0.631 (95% CI 0.425–0.937); p = 0.022). Regarding the symptoms associated with depression, we evaluated the impact of the ADORA2A SNP in the occurrence of sad/discouraged mood, anhedonia, appetite changes, sleep disturbances, motion changes, energy loss, feelings of worthless or guilty, difficulty in concentrating, and presence of bad thoughts. Notably, the TT genotype was independently associated with reduced sleep disturbances (OR = 0.438 (95% CI 0.258–0.743); p = 0.002) and less difficulty in concentrating (OR = 0.534 (95% CI 0.316–0.901; p = 0.019). The cross-sectional design cannot evaluate the cause-effect relationship and did not evaluate the functional consequences of this polymorphism. Our data support an important role for ADORA2A rs2298383 SNP in clinical heterogeneity associated with depression. The presence of the TT genotype was associated with decrease risk for current depression and disturbances in sleep and attention, two of the most common symptoms associated with this disorder.

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Funding

This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES), and Programa de Apoio a Núcleos de Excelência-Fundação de Amparo a Pesquisa do Estado do Rio Grande do Sul (PRONEX-FAPERGS 08/2009 - Pronex 10/0055-0). RAS, KJ, LDMS, and MPK are CNPq Research Fellows. APA and CRB receive a fellowship from CAPES.

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Authors and Affiliations

  1. Department of Life and Health Sciences, Catholic University of Pelotas, Pelotas, Rio Grande do Sul, Brazil

    Sílvia Oliveira, Ana Paula Ardais, Clarissa Ribeiro Bastos, Marta Gazal, Karen Jansen, Luciano de Mattos Souza, Ricardo Azevedo da Silva & Gabriele Ghisleni

  2. Biology Laboratory, University of Campanha Region, Bagé, Rio Grande do Sul, Brazil

    Sílvia Oliveira

  3. Laboratório de Neurociências Clínicas, Programa de Pós-Graduação em Saúde e Comportamento, Universidade Católica de Pelotas (UCPel), Rua Gonçalves Chaves 373, sala 324C, Pelotas, RS, 96015-560, Brazil

    Ana Paula Ardais

  4. Department of Biochemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil

    Manuella Pinto Kaster

  5. Department of Cellular and Molecular Biology, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil

    Diogo Rizzato Lara

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  1. Sílvia Oliveira
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Contributions

All authors mentioned in the paper have significantly contributed to the research. RAS, KJ, LDMS, and DRL conceived and supervised the clinical evaluation. MPK and GG and supervised the collection and processing of biological samples. CRB and SO performed the DNA extraction and genotyping. SO, APA, GG, and MPK performed the statistical analysis and wrote the article. All authors approved the final manuscript.

Corresponding author

Correspondence to Ana Paula Ardais.

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Conflicts of interest

Sílvia Oliveira declares no conflict of interest.

Ana Paula Ardais declares no conflict of interest.

Clarissa Ribeiro Bastos declares no conflict of interest.

Marta Gazal declares no conflict of interest.

Karen Jansen declares no conflict of interest.

Luciano de Mattos Souza declares no conflict of interest.

Ricardo Azevedo da Silva declares no conflict of interest.

Manuella Pinto Kaster declares no conflict of interest.

Diogo Rizzato Lara declares no conflict of interest.

Gabriele Ghisleni declares no conflict of interest.

Ethical approval

The study was approved by the Ethical Committee of the Catholic University of Pelotas, Brazil (protocol number 2010/15), and all participants signed the informed consent.

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Oliveira, S., Ardais, A.P., Bastos, C.R. et al. Impact of genetic variations in ADORA2A gene on depression and symptoms: a cross-sectional population-based study. Purinergic Signalling 15, 37–44 (2019). https://doi.org/10.1007/s11302-018-9635-2

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