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Influence of GSTP1 rs1695 polymorphism on survival in male patients’ amyotrophic lateral sclerosis: a genetic association study in Brazilian population

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Abstract

Background

Glutathione S-transferase Pi (GSTP1) enzyme has a major antioxidant effect on the central nervous system (CNS), where it acts against oxidative damage, an established risk factor for amyotrophic lateral sclerosis (ALS). Hence, the purpose of this study was to evaluate a possible relationship between GSTP1 rs1695 polymorphism and the survival rate of male ALS patients, which is the gender more affected by the disease.

Methods and results

A case-control study was performed with 56 male ALS patients and 70 healthy male individuals from Midwestern Brazil, which were age-adjusted. GSTP1 rs1695 polymorphism molecular analysis was carried out with restriction fragment length polymorphism. The relationship between ALS patients and GSTP1 rs1695 polymorphism was analyzed using cumulative survival rate as the major outcome, where differences in survival were evaluated through the log-rank test. Our results revealed that mutant genotype (G/G) did not influence the cumulative survival rate of male ALS patients regarding the age of diagnosis (p = 0.5) and time from symptom to diagnosis (p = 0.3). On the other hand, mutant carriers exhibited a significant survival of fewer than 25 months compared to A/A and A/G genotypes that survive more than 100 months (p = 7−E10) in comparison with symptom onset to outcome (p = 0.00006).

Conclusions

In summary, our findings revealed that mutant genotype carriers’ male patients had a reduced lifetime, which probably may be resulted from oxidative stress exposure in CNS.

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Data availability

Available.

Code availability

These data are available upon request to the Research Ethics Committee - Federal University of Goiás, Goiânia, Goiás, Brazil by e-mail: cep.prpi@ufg.br.

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Acknowledgements

The authors are thankful to the Rehabilitation and Readaptation Medical Center Dr. Henrique Santillo (CRER) and the Clinics Hospital of the Federal University of Goiás, for allowing the collection of the study samples.

Funding

No funding was received for conducting this study.

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Authors and Affiliations

Authors

Contributions

Conceptualization: DCPB, RSS, AASR. Methodology, Validation, Project administration, Resources, Supervision and Visualization: RSS, AASR. Data Curation and Investigation: JBSB, KFS, DCPB, RSS, AASR. Software analysis: LPA. Formal analysis: JBSB, LPA. Writing original draft, review & editing: JBSB, RSS, AASR.

Corresponding authors

Correspondence to Rodrigo da Silva Santos or Angela Adamski da Silva Reis.

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Conflict of interest

All the authors declare that they have no conflict of interest to declare.

Ethical approval

This work was approved by the Ethical Committee of the Federal University of Goiás (Number CAAE 79593117.7.0000.5083) and followed the principles exposed in declaration of Helsinki.

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All participants agree with the study and signed the informed consent allowing their data publication.

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de Sousa Barros, J.B., de Faria Santos, K., da Cruz Pereira Bento, D. et al. Influence of GSTP1 rs1695 polymorphism on survival in male patients’ amyotrophic lateral sclerosis: a genetic association study in Brazilian population. Mol Biol Rep 49, 1655–1659 (2022). https://doi.org/10.1007/s11033-021-06724-z

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