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.
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.
References
Volonté C, Apolloni S, Sabatelli M (2019) Histamine beyond its effects on allergy: potential therapeutic benefits for the treatment of amyotrophic lateral sclerosis (ALS). Pharmacol Ther 202:120–131. https://doi.org/10.1016/j.pharmthera.2019.06.006
Riancho J, Bosque-Varela P, Perez-Pereda S et al (2018) The increasing importance of environmental conditions in amyotrophic lateral sclerosis. Int J Biometeorol 62:1361–1374. https://doi.org/10.1007/s00484-018-1550-2
Eum K-D, Seals RM, Taylor KM et al (2015) Modification of the association between lead exposure and amyotrophic lateral sclerosis by iron and oxidative stress related gene polymorphisms. Amyotroph Lateral Scler Frontotemporal Degener 16:72–79. https://doi.org/10.3109/21678421.2014.964259
D’Amico E, Factir-Litvak P, Santella RM, Mitsumoto H (2013) Clinical perspective of oxidative stress in sporadic ALS. Free Radic Biol Med 65:509–527. https://doi.org/10.1016/j.freeradbiomed.2013.06.029
Gajewska B, Kaźmierczak B, Kuźma-Kozakiewicz M et al (2015) GSTP1 polymorphisms and their association with glutathione transferase and peroxidase activities in patients with motor neuron disease. CNS Neurol Disord Drug Targets 14:1328–1333. https://doi.org/10.2174/1871527314666150821104019
Kaźmierczak B, Kuźma-Kozakiewicz M, Usarek E, Barańczyk-Kuźma A (2011) Differences in glutathione S-transferase pi expression in transgenic mice with symptoms of neurodegeneration. Acta Biochim Pol 58:621–626. https://doi.org/10.18388/abp.2011_2233
Zherebtsova AL, Shadrina MI, Levitsky GN et al (2004) Analysis of the glutathione S-transferase P1 gene Ile105Val polymorphism in the patients with sporadic motor neuron disease from Russia. Russ J Genet 40:691–693. https://doi.org/10.1023/B:RUGE.0000033319.46071.84
de Sousa Barros JB, de Faria Santos K, Azevedo RM et al (2021) No association of GSTP1 rs1695 polymorphism with amyotrophic lateral sclerosis: a case–control study in the Brazilian population. PLoS ONE 16:1–15. https://doi.org/10.1371/journal.pone.0247024
Little J, Higgins JPT, Ioannidis JPA et al (2009) STrengthening the REporting of Genetic Association studies (STREGA): an extension of the STROBE statement. Genet Epidemiol 33:581–598. https://doi.org/10.1002/gepi.20410
Usarek E, Gajewska B, Kaźmierczak B et al (2005) A study of glutathione S-transferase pi expression in central nervous system of subjects with amyotrophic lateral sclerosis using RNA extraction from formalin-fixed, paraffin-embedded material. Neurochem Res 30:1003–1007. https://doi.org/10.1007/s11064-005-6771-1
Kuźma M, Jamrozik Z, Barańczyk-Kuźma A (2006) Activity and expression of glutathione S-transferase pi in patients with amyotrophic lateral sclerosis. Clin Chim Acta 364:217–221. https://doi.org/10.1016/j.cccn.2005.07.008
Blasco H, Guennoc AM, Veyrat-Durebex C et al (2012) Amyotrophic lateral sclerosis: a hormonal condition? Amyotroph Lateral Scler 13:585–588. https://doi.org/10.3109/17482968.2012.706303
Aggarwal T, Polanco MJ, Scaramuzzino C et al (2014) Androgens affect muscle, motor neuron, and survival in a mouse model of SOD1-related amyotrophic lateral sclerosis. Neurobiol Aging 35:1929–1938. https://doi.org/10.1016/j.neurobiolaging.2014.02.004
McCombe PA, Henderson RD (2010) Effects of gender in amyotrophic lateral sclerosis. Gend Med 7:557–570. https://doi.org/10.1016/j.genm.2010.11.010
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.
Author information
Authors and Affiliations
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
Ethics declarations
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.
Consent to participate and for publication
All participants agree with the study and signed the informed consent allowing their data publication.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-021-06724-z