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Caffeine Consumption and Interaction with ADORA2A, CYP1A2 and NOS1 Variants Do Not Influence Age at Onset of Machado-Joseph Disease

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Abstract

Background

The age at onset (AO) of Machado-Joseph disease (SCA3/MJD), a disorder due to an expanded CAG repeat (CAGexp) in ATXN3, is quite variable and the role of environmental factors is still unknown. Caffeine was associated with protective effects against other neurodegenerative diseases, and against SCA3/MJD in transgenic mouse models. We aimed to evaluate whether caffeine consumption and its interaction with variants of caffeine signaling/metabolization genes impact the AO of this disease.

Methods

a questionnaire on caffeine consumption was applied to adult patients and unrelated controls living in Rio Grande do Sul, Brazil. AO and CAGexp were previously determined. SNPs rs5751876 (ADORA2A), rs2298383 (ADORA2A), rs762551 (CYP1A2) and rs478597 (NOS1) were genotyped. AO of subgroups were compared, adjusting the CAGexp to 75 repeats (p < 0.05).

Results

171/179 cases and 98/100 controls consumed caffeine. Cases with high and low caffeine consumption (more or less than 314.5 mg of caffeine/day) had mean (SD) AO of 35.05 (11.44) and 35.43 (10.08) years (p = 0.40). The mean (SD) AO of the subgroups produced by the presence or absence of caffeine-enhancing alleles in ADORA2A (T allele at rs5751876 and rs2298383), CYP1A2 (C allele) and NOS1 (C allele) were all similar (p between 0.069 and 0.516).

Discussion

Caffeine consumption was not related to changes in the AO of SCA3/MJD, either alone or in interaction with protective genotypes at ADORA2A, CYP1A2 and NOS1.

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Data Availability

The data that support the findings of this study have been deposited in OSF, link https://osf.io/3h6v7/.

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Acknowledgements

We are grateful to all study participants. This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil, grant number 405963/2021-1; and by Financiamento e Incentivo à Pesquisa, Hospital de Clínicas de Porto Alegre (FIPE HCPA) grants numbers 2018-0660 and 2018-0661. ACM, JSP, LS, ERC, DS, LDP, BAA, MLSP and LBJ were supported by CNPq.

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Authors and Affiliations

  1. Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, Porto Alegre, 91501-970, Brazil

    Ana Carolina Martins, Maria Luiza Saraiva-Pereira & Laura Bannach Jardim

  2. Centros de Pesquisa Clínica e Experimental, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Porto Alegre, 90035-903, Brazil

    Ana Carolina Martins, Jordânia dos Santos Pinheiro, Luciana Szinwelski, Eduardo Rockenbach Cidade, Danilo Fernando Santin, Laura Damke Proença, Bruna Almeida Araújo, Maria Luiza Saraiva-Pereira & Laura Bannach Jardim

  3. Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, 90610-000, Brazil

    Jordânia dos Santos Pinheiro & Luciana Szinwelski

  4. Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2400, Porto Alegre, 90.035-002, Brazil

    Eduardo Rockenbach Cidade, Danilo Fernando Santin & Laura Bannach Jardim

  5. Instituto de Biociências , Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves 9500, Porto Alegre, 91501-970, Brazil

    Laura Damke Proença

  6. Curso de Biomedicina, Universidade Federal do Rio Grande do Sul, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600, Porto Alegre, 90035-003, Brazil

    Bruna Almeida Araújo

  7. Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Porto Alegre, 90035-903, Brazil

    Maria Luiza Saraiva-Pereira & Laura Bannach Jardim

  8. Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600, Porto Alegre, 90035-003, Brazil

    Maria Luiza Saraiva-Pereira

  9. Departamento de Medicina Interna, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2400, Porto Alegre, 90.035-002, Brazil

    Laura Bannach Jardim

  10. DMI FAMED UFRGS, Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Porto Alegre, 90035-003, Brazil

    Laura Bannach Jardim

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  1. Ana Carolina Martins
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  2. Jordânia dos Santos Pinheiro
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Contributions

A.C.M and L.B.J. contributed to the conception and design of the study; A.C.M, J.S.P., L.S., E.R.C., D.F.S., L.D.P., B.A.A., M.L.S.P., and L.B.J. contributed to the acquisition and analysis of data; A.C.M. and L.B.J. contributed to drafting the text and preparing the tables. All authors reviewed the manuscript.

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Correspondence to Laura Bannach Jardim.

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Martins, A.C., Pinheiro, J.d.S., Szinwelski, L. et al. Caffeine Consumption and Interaction with ADORA2A, CYP1A2 and NOS1 Variants Do Not Influence Age at Onset of Machado-Joseph Disease. Cerebellum (2024). https://doi.org/10.1007/s12311-024-01717-7

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