DOI: 10.1007/s12017-016-8416-8 Pages: 41-45
Article Type: Original Paper

Promoter Variation and Expression Levels of Inflammatory Genes IL1A, IL1B, IL6 and TNF in Blood of Spinocerebellar Ataxia Type 3 (SCA3) Patients

1. University of the Azores, Department of Biology

2. Universidade do Porto, Instituto de Investigação e Inovação em Saúde

3. University of Porto, Institute for Molecular and Cell Biology (IBMC)

4. UCL Institute of Neurology, Department of Clinical and Experimental Epilepsy

5. UCL Institute of Neurology, Department of Molecular Neuroscience

6. Hospital do Divino Espírito Santo, Department of Neurology

7. Hospital of D. Estefania, Department of Clinical Genetics

8. Hospital do Santo Espírito da Ilha Terceira, SEEBMO

Correspondence to:
Mafalda Raposo
Tel: +351 296650476



Age at onset in spinocerebellar ataxia type 3 (SCA3/MJD) is incompletely explained by the size of the CAG tract at the ATXN3 gene, implying the existence of genetic modifiers. A role of inflammation in SCA3 has been postulated, involving altered cytokines levels; promoter variants leading to alterations in cytokines expression could influence onset. Using blood from 86 SCA3 patients and 106 controls, this work aimed to analyse promoter variation of four cytokines (IL1A, IL1B, IL6 and TNF) and to investigate the association between variants detected and their transcript levels, evaluated by quantitative PCR. Moreover, the effect of APOE isoforms, known to modulate cytokines, was investigated. Correlations between cytokine variants and onset were tested; the cumulative modifier effects of cytokines and APOE were analysed. Patients carrying the IL6*C allele had a significant earlier onset (4 years in average) than patients carrying the G allele, in agreement with lower mRNA levels produced by IL6*C carriers. The presence of APOE*ɛ2 allele seems to anticipate onset in average 10 years in patients carrying the IL6*C allele; a larger number of patients will be needed to confirm this result. These results highlight the pertinence of conducting further research on the role of cytokines as SCA3 modulators, pointing to the presence of shared mechanisms involving IL6 and APOE.

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  • Accepted: May 25, 2016
  • Online: May 31, 2016

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