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

Area of Science:

• Biochemistry
• Genetics
• Nutritional Science

Background:

• Glutathione peroxidase 1 (GPx1) is a crucial antioxidant selenoenzyme protecting cells from reactive oxygen species.
• GPx1 activity is dependent on selenium (Se) concentration, with a known genetic polymorphism (Pro198Leu) potentially affecting its function.
• Previous in vitro studies suggested the GPx1 Leu allele may reduce enzyme responsiveness to selenium.

Purpose of the Study:

• To investigate whether the GPx1 Pro198Leu polymorphism influences GPx1 enzyme activity in relation to selenium status in healthy individuals.
• To assess the functional significance of GPx1 polymorphism in the human body concerning selenium metabolism.

Main Methods:

• Studied 405 healthy individuals of Polish origin.
• Measured red blood cell GPx1 activity using spectrophotometry.
• Quantified plasma selenium concentration via graphite furnace atomic absorption spectrometry.
• Genotyped the GPx1 Pro198Leu polymorphism using Molecular Beacon Real-Time PCR.

Main Results:

• No significant differences in mean plasma selenium or GPx1 activity were observed between different GPx1 genotypes.
• However, the correlation between GPx1 activity and selenium concentration varied significantly across genotypes.
• A stronger positive correlation was found for Pro/Pro (r=0.44) and Pro/Leu (r=0.35) genotypes compared to Leu/Leu (r=0.25), with a statistically significant difference between Pro/Pro and Leu/Leu groups (p=0.034).

Conclusions:

• The GPx1 Pro198Leu polymorphism demonstrates functional significance in humans, affecting GPx1 activity's response to selenium levels.
• These findings support in vitro observations and underscore the importance of considering genetic background when using selenoprotein biomarkers like GPx1 activity to assess selenium status.