Objective: To assess the impact of the GSTM1 and GSTT1 null genotypes on clinical severity and genomic instability in a large cohort of patients with SCA2.

Background: Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder caused by a CAG repeat expansion mutation in the ATXN2 gene. Disease severity is largely determined by the repeat length, though a few additional modifier genes have been identified in candidate gene studies.

Method: A study involving 303 Cuban SCA2 patients and 103 control individuals was conducted. The ATXN2 CAG repeat length was determined by PCR followed by polyacrylamide gel electrophoresis. GSTM1 and GSTT1 null genotypes were assessed by PCR followed by agarose gel electrophoresis. The frequency of micronuclei and nuclear bridges was determined in exfoliated buccal cells using Feulgen stain. The age at disease onset, SARA, and INAS scores were used as clinical outcome variables.

Results: No significant differences were observed between patients and controls for the frequency of GSTM1 and GSTT1 null genotypes or genotype combinations. The GSTT1 null genotype was associated with higher SARA score and INAS count in univariate analysis, but these effects lost significance after adjusting for the CAG repeat length and disease duration. GSTM1 and GSTT1 null genotypes were not associated with the frequency of micronuclei and nuclear bridges.

Conclusion: GSTM1 and GSTT1 null genotypes do not have a clear impact on clinical severity or genomic instability in Cuban patients with SCA2. Further studies in additional SCA2 cohorts are needed to account for the potential effects of population structure.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/gstm1-and-gstt1-null-genotypes-as-candidate-modifiers-of-clinical-severity-and-genomic-instability-in-cuban-patients-with-spinocerebellar-ataxia-type-2/