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

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 relation...

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Veröffentlicht in:Molecular biology reports 2022-02, Vol.49 (2), p.1655-1659
Hauptverfasser: de Sousa Barros, Jéssica Barletto, de Faria Santos, Kamilla, da Cruz Pereira Bento, Dhiogo, Prado Assunção, Leandro do, da Silva Santos, Rodrigo, da Silva Reis, Angela Adamski
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container_issue 2
container_start_page 1655
container_title Molecular biology reports
container_volume 49
creator de Sousa Barros, Jéssica Barletto
de Faria Santos, Kamilla
da Cruz Pereira Bento, Dhiogo
Prado Assunção, Leandro do
da Silva Santos, Rodrigo
da Silva Reis, Angela Adamski
description 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.
doi_str_mv 10.1007/s11033-021-06724-z
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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.</description><identifier>ISSN: 0301-4851</identifier><identifier>EISSN: 1573-4978</identifier><identifier>DOI: 10.1007/s11033-021-06724-z</identifier><identifier>PMID: 34623592</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Adult ; Amyotrophic lateral sclerosis ; Amyotrophic Lateral Sclerosis - genetics ; Amyotrophic Lateral Sclerosis - metabolism ; Animal Anatomy ; Animal Biochemistry ; Antioxidants ; Biomedical and Life Sciences ; Brazil - epidemiology ; Case-Control Studies ; Central nervous system ; Diagnosis ; Gene polymorphism ; Genetic Association Studies - methods ; Genetic Predisposition to Disease ; Genotype ; Glutathione S-Transferase pi - genetics ; Glutathione S-Transferase pi - metabolism ; Glutathione transferase ; Histology ; Humans ; Life Sciences ; Male ; Middle Aged ; Morphology ; Mutants ; Oxidative stress ; Polymorphism ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide - genetics ; Population studies ; Rapid Communication ; Restriction fragment length polymorphism ; Risk Factors ; Survival</subject><ispartof>Molecular biology reports, 2022-02, Vol.49 (2), p.1655-1659</ispartof><rights>The Author(s), under exclusive licence to Springer Nature B.V. 2021</rights><rights>2021. 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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.</description><subject>Adult</subject><subject>Amyotrophic lateral sclerosis</subject><subject>Amyotrophic Lateral Sclerosis - genetics</subject><subject>Amyotrophic Lateral Sclerosis - metabolism</subject><subject>Animal Anatomy</subject><subject>Animal Biochemistry</subject><subject>Antioxidants</subject><subject>Biomedical and Life Sciences</subject><subject>Brazil - epidemiology</subject><subject>Case-Control Studies</subject><subject>Central nervous system</subject><subject>Diagnosis</subject><subject>Gene polymorphism</subject><subject>Genetic Association Studies - methods</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotype</subject><subject>Glutathione S-Transferase pi - genetics</subject><subject>Glutathione S-Transferase pi - metabolism</subject><subject>Glutathione transferase</subject><subject>Histology</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Morphology</subject><subject>Mutants</subject><subject>Oxidative stress</subject><subject>Polymorphism</subject><subject>Polymorphism, Restriction Fragment Length</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Population studies</subject><subject>Rapid Communication</subject><subject>Restriction fragment length polymorphism</subject><subject>Risk Factors</subject><subject>Survival</subject><issn>0301-4851</issn><issn>1573-4978</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kc1u1DAUhS0EokPhBVggS2zYBPxvhx2toFSqBBJlbTnJTXHl2MFOKs2seI2-Hk-Cp1NAYsHKi_Odc33vQeg5Ja8pIfpNoZRw3hBGG6I0E83uAdpQqXkjWm0eog3hhDbCSHqEnpRyTQgRVMvH6IgLxbhs2QbdnscxrBB7wGnEZ18uP1OcC1WtxHMK2ynl-ZsvE04RlzXf-BsXsI94cgHw7BYPcSk_f9xiN23TklOFexzcArlypQ-QU_HlLXb4CiIsVXSlpN5X5z5xWYftPu4ku50P3sU6dF7DnfoUPRpdKPDs_j1GXz-8vzz92Fx8Ojs_fXfR9FzLpZHD2Lacam5aML0Rko0DFx0Y03IliOugg5Fr41jXO8elUE47NRjtRqUJU_wYvTrkzjl9X6EsdvKlhxBchLQWy6Qh9RxKi4q-_Ae9TmuO9XeWKab2V2eyUuxA9XX5kmG0c_aTy1tLid0XZw_F2VqcvSvO7qrpxX302k0w_LH8bqoC_ACUKsUryH9n_yf2F-Q8pzI</recordid><startdate>20220201</startdate><enddate>20220201</enddate><creator>de Sousa Barros, Jéssica Barletto</creator><creator>de Faria Santos, Kamilla</creator><creator>da Cruz Pereira Bento, Dhiogo</creator><creator>Prado Assunção, Leandro do</creator><creator>da Silva Santos, Rodrigo</creator><creator>da Silva Reis, Angela Adamski</creator><general>Springer Netherlands</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8895-2628</orcidid><orcidid>https://orcid.org/0000-0002-8281-7334</orcidid><orcidid>https://orcid.org/0000-0002-0555-3072</orcidid><orcidid>https://orcid.org/0000-0002-1743-8151</orcidid><orcidid>https://orcid.org/0000-0002-0377-3004</orcidid><orcidid>https://orcid.org/0000-0002-9480-4362</orcidid></search><sort><creationdate>20220201</creationdate><title>Influence of GSTP1 rs1695 polymorphism on survival in male patients’ amyotrophic lateral sclerosis: a genetic association study in Brazilian population</title><author>de Sousa Barros, Jéssica Barletto ; 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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.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>34623592</pmid><doi>10.1007/s11033-021-06724-z</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0001-8895-2628</orcidid><orcidid>https://orcid.org/0000-0002-8281-7334</orcidid><orcidid>https://orcid.org/0000-0002-0555-3072</orcidid><orcidid>https://orcid.org/0000-0002-1743-8151</orcidid><orcidid>https://orcid.org/0000-0002-0377-3004</orcidid><orcidid>https://orcid.org/0000-0002-9480-4362</orcidid></addata></record>
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subjects Adult
Amyotrophic lateral sclerosis
Amyotrophic Lateral Sclerosis - genetics
Amyotrophic Lateral Sclerosis - metabolism
Animal Anatomy
Animal Biochemistry
Antioxidants
Biomedical and Life Sciences
Brazil - epidemiology
Case-Control Studies
Central nervous system
Diagnosis
Gene polymorphism
Genetic Association Studies - methods
Genetic Predisposition to Disease
Genotype
Glutathione S-Transferase pi - genetics
Glutathione S-Transferase pi - metabolism
Glutathione transferase
Histology
Humans
Life Sciences
Male
Middle Aged
Morphology
Mutants
Oxidative stress
Polymorphism
Polymorphism, Restriction Fragment Length
Polymorphism, Single Nucleotide - genetics
Population studies
Rapid Communication
Restriction fragment length polymorphism
Risk Factors
Survival
title Influence of GSTP1 rs1695 polymorphism on survival in male patients’ amyotrophic lateral sclerosis: a genetic association study in Brazilian population
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