Interaction between genes, caffeine and tobacco use as factors for the onset of Machado-Joseph disease/Spinocerebellar Ataxia Type 3

- Compare consumption habits (caffeine, tobacco and others) in different SCA3/MJD populations and to study the possible role of these factors on the modulation of age of onset in SCA3 / MJD.

The expanded CAG repeat at ATXN3 is the unique cause of spinocerebellar ataxia (SCA) type 3, also known as Machado-Joseph disease (SCA3/MJD). Besides that, the size of expansion determines 55% of the variability in the age of onset (AO) of symptoms. In a recent meta-analysis, we estimated that the sum of other factors - geographic origin, family factors, the normal CAG repeat at ATXN2 - can explain up to 73.5% of the age variation of onset of the disease (PMID: 30337442). This suggests that part of the remaining 26.5% in AO variability may not be hereditary. Portuguese and Azorean migrations, mainly in 18th and 19th centuries, determined new SCA3/MJD founder effects in Brazil and Canada. For instance, the probable genetic distance between SCA3/MJD populations of Azores and Brazilian should be of 10 to 12 generations; the distance between the Azorean and Canadian SCA3/MJD populations can be even smaller.

We intend to take advantage of the genetic proximity and of the great environmental differences between these populations, to compare their consumption habits (caffeine, tobacco and others) and to study their possible role on the modulation of AO in SCA3 / MJD.

Cohorts used SCA3 in Canada and Brazil
Funding available? To be sought
Trial readiness category 1:   basic prerequisites for trial readiness

Contact persons:
Laura Bannach Jardim
Universidade Federal do Rio Grande do Sul, Porte Alegre, Brazil

Further project partners:
Orlando Barsottini
Universidade Federal de São Paulo, São Paulo, Brazil
Joana Damásio
Hospital Santo Antonio, Porto, Portugal
Marcondes França Jr
Universidade Estadual de Campinas, Campinas, Brazil
Wilson Marques Junior
Universidade de São Paulo, Ribeirão Preto, Brazil
Maria Manuela Medeiros Lima
Universidade dos Açores, Ponta Delgada, Portugal
Renato Munhoz
University of Toronto, Toronto, Canada
Luis Pereira de Almeida
Universidade de Coimbra, Coimbra, Portugal
José Luiz Pedroso
Universidade Federal de São Paulo, São Paulo, Brazil