Association between GPx1 Pro198Leu polymorphism, GPx1 activity and plasma selenium concentration in humans.

2.50
Hdl Handle:
http://hdl.handle.net/10146/113554
Title:
Association between GPx1 Pro198Leu polymorphism, GPx1 activity and plasma selenium concentration in humans.
Authors:
Jablonska, E. ( 0000-0002-3946-3964 ) ; Gromadzinska, J.; Reszka, E. ( 0000-0003-2153-4864 ) ; Wasowicz, W. ( 0000-0002-2991-9040 ) ; Sobala, W. ( 0000-0002-5451-9321 ) ; Szeszenia-Dabrowska, N. ( 0000-0001-5307-7720 ) ; Boffetta, P.
Abstract:
BACKGROUND: Glutathione peroxidase 1 (GPx1) is an antioxidant selenoenzyme that protects the cells against reactive oxygen species. Its activity depends on the concentration of selenium (Se) which is present in the active centre of the enzyme. The genetic polymorphism of GPx1 encoding gene (GPx1) associated with the proline (Pro) to leucine (Leu) change at codon 198 is supposed to be functional. An in vitro study performed on human breast carcinoma cell line showed that GPx1Leu allele was associated with a lower responsiveness of the enzyme to Se added to the culture medium. Some authors observed a decrease in GPx1 activity associated with GPx1 Leu allele in humans; however, there were no findings on how GPx1 activity changes with Se concentration in individuals with different GPx1 genotypes. AIM OF THE STUDY: To assess whether GPx1 activity that depends on the Se status may be influenced by GPx1 polymorphism through studying this relationship in the blood of healthy individuals. METHODS: The association between the Se status, GPx1 activity and GPx1 genotype was assessed in 405 individuals of Polish origin. GPx1 activity in red blood cells was measured by the spectrophotometric method by Paglia and Valentine, using t-butylhydroperoxide as the substrate. Plasma Se concentration was measured using graphite furnace atomic absorption spectrometry. GPx1 Pro198Leu polymorphism was determined with the Molecular Beacon Real-Time PCR assay. RESULTS: In the subjects examined, the mean plasma Se concentration was 54.4 +/- 14.2 mcg/L. The mean GPx1 activity was 15.1 +/- 4.7 U/g Hb. No difference regarding both the parameters was found between individuals with different GPx1 genotype. However, the association between GPx1 activity and Se concentration, analyzed separately for each genotype group, was not the same. The correlation coefficients amounted to r = 0.44 (p < 0.001) for Pro/Pro, r = 0.35 (p < 0.001) for Pro/Leu and r = 0.25 (p = 0.45) for Leu/Leu group, which indicates that the correlation strength was as follows: Pro/Pro > Pro/Leu > Leu/Leu. Notably, statistically significant difference in this relationship (analyzed as difference between correlation coefficients for linear trends) was found between genotypes Pro/Pro and Leu/Leu (p = 0.034). CONCLUSIONS: The findings of the present study provide evidence for the hypothesis based on in vitro studies which assumes that GPx1 Pro198Leu polymorphism has a functional significance for the human organism and that this functionality is associated with a different response of GPx1 activity to Se. They also point to the importance of the genetic background in the assessment of the Se status with the use of selenoprotein biomarkers such as GPx1 activity.
Citation:
Eur. J. Nutr. 2009, 48 (6):383-386
Journal:
European Journal of Nutrition
Issue Date:
Sep-2009
URI:
http://hdl.handle.net/10146/113554
DOI:
10.1007/s00394-009-0023-0
PubMed ID:
19415410
Additional Links:
http://www.springerlink.com/content/p06mg711516428h2/
Type:
Article
Language:
en
ISSN:
1436-6215
Sponsors:
This study was supported by ECNIS NoE (Contract No. 513943/UE), internal grant IMP 1.3/2008 and IARC multicentre case-control study of lung cancer (Contract No. IC15- CT96-0313).
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorJablonska, E.en
dc.contributor.authorGromadzinska, J.en
dc.contributor.authorReszka, E.en
dc.contributor.authorWasowicz, W.en
dc.contributor.authorSobala, W.en
dc.contributor.authorSzeszenia-Dabrowska, N.en
dc.contributor.authorBoffetta, P.en
dc.date.accessioned2010-10-20T13:40:52Zen
dc.date.available2010-10-20T13:40:52Zen
dc.date.issued2009-09en
dc.identifier.citationEur. J. Nutr. 2009, 48 (6):383-386en
dc.identifier.issn1436-6215en
dc.identifier.pmid19415410en
dc.identifier.doi10.1007/s00394-009-0023-0en
dc.identifier.urihttp://hdl.handle.net/10146/113554en
dc.description.abstractBACKGROUND: Glutathione peroxidase 1 (GPx1) is an antioxidant selenoenzyme that protects the cells against reactive oxygen species. Its activity depends on the concentration of selenium (Se) which is present in the active centre of the enzyme. The genetic polymorphism of GPx1 encoding gene (GPx1) associated with the proline (Pro) to leucine (Leu) change at codon 198 is supposed to be functional. An in vitro study performed on human breast carcinoma cell line showed that GPx1Leu allele was associated with a lower responsiveness of the enzyme to Se added to the culture medium. Some authors observed a decrease in GPx1 activity associated with GPx1 Leu allele in humans; however, there were no findings on how GPx1 activity changes with Se concentration in individuals with different GPx1 genotypes. AIM OF THE STUDY: To assess whether GPx1 activity that depends on the Se status may be influenced by GPx1 polymorphism through studying this relationship in the blood of healthy individuals. METHODS: The association between the Se status, GPx1 activity and GPx1 genotype was assessed in 405 individuals of Polish origin. GPx1 activity in red blood cells was measured by the spectrophotometric method by Paglia and Valentine, using t-butylhydroperoxide as the substrate. Plasma Se concentration was measured using graphite furnace atomic absorption spectrometry. GPx1 Pro198Leu polymorphism was determined with the Molecular Beacon Real-Time PCR assay. RESULTS: In the subjects examined, the mean plasma Se concentration was 54.4 +/- 14.2 mcg/L. The mean GPx1 activity was 15.1 +/- 4.7 U/g Hb. No difference regarding both the parameters was found between individuals with different GPx1 genotype. However, the association between GPx1 activity and Se concentration, analyzed separately for each genotype group, was not the same. The correlation coefficients amounted to r = 0.44 (p < 0.001) for Pro/Pro, r = 0.35 (p < 0.001) for Pro/Leu and r = 0.25 (p = 0.45) for Leu/Leu group, which indicates that the correlation strength was as follows: Pro/Pro > Pro/Leu > Leu/Leu. Notably, statistically significant difference in this relationship (analyzed as difference between correlation coefficients for linear trends) was found between genotypes Pro/Pro and Leu/Leu (p = 0.034). CONCLUSIONS: The findings of the present study provide evidence for the hypothesis based on in vitro studies which assumes that GPx1 Pro198Leu polymorphism has a functional significance for the human organism and that this functionality is associated with a different response of GPx1 activity to Se. They also point to the importance of the genetic background in the assessment of the Se status with the use of selenoprotein biomarkers such as GPx1 activity.en
dc.description.sponsorshipThis study was supported by ECNIS NoE (Contract No. 513943/UE), internal grant IMP 1.3/2008 and IARC multicentre case-control study of lung cancer (Contract No. IC15- CT96-0313).en
dc.language.isoenen
dc.relation.urlhttp://www.springerlink.com/content/p06mg711516428h2/en
dc.subjectSmokingen
dc.subjectSex Factorsen
dc.subjectPolymorphismen
dc.subjectBiological Markersen
dc.subjectHumansen
dc.subjectGenotypeen
dc.subjectGlutathione Peroxidaseen
dc.subjectErythrocytesen
dc.subjectAgingen
dc.subjectAllelesen
dc.subjectSeleniumen
dc.subjectPolanden
dc.subject.meshAgeden
dc.subject.meshAgingen
dc.subject.meshAllelesen
dc.subject.meshBiological Markersen
dc.subject.meshCodonen
dc.subject.meshErythrocytesen
dc.subject.meshFemaleen
dc.subject.meshGenotypeen
dc.subject.meshGlutathione Peroxidaseen
dc.subject.meshHumansen
dc.subject.meshLinear Modelsen
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshPolanden
dc.subject.meshPolymorphism, Geneticen
dc.subject.meshResearch Designen
dc.subject.meshSeleniumen
dc.subject.meshSex Factorsen
dc.subject.meshSmokingen
dc.titleAssociation between GPx1 Pro198Leu polymorphism, GPx1 activity and plasma selenium concentration in humans.en
dc.typeArticleen
dc.identifier.journalEuropean Journal of Nutritionen

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