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


OBJECTIVE
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.
Jablonska
E
E
Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz, Poland. ewa@imp.lodz.pl
Gromadzinska
J
J
Reszka
E
E
Wasowicz
W
W
Sobala
W
W
Szeszenia-Dabrowska
N
N
Boffetta
P
P
D000368:Aged; D000375:Aging; D000483:Alleles; D015415:Biomarkers / Q000097:blood; D003062:Codon; D004912:Erythrocytes / Q000737:chemistry; D005260:Female; D005838:Genotype; D005979:Glutathione Peroxidase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011044:Poland; D011110:Polymorphism, Genetic; D012107:Research Design; D012643:Selenium / Q000097:blood*; D012737:Sex Factors; D012907:Smoking; D000094765:Glutathione Peroxidase GPX1
D015415:Biomarkers; D003062:Codon; D005979:Glutathione Peroxidase; D012643:Selenium; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human