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Influence of the glutathione peroxidase 1 Pro200Leu polymorphism on the response of glutathione peroxidase activity to selenium supplementation: a randomized controlled trial.
Am J Clin Nutr. 2012 Oct; 96(4):923-31.AJ

Abstract

BACKGROUND

A genetic variant at codon 200 (Pro200Leu) of the gene encoding for glutathione peroxidase 1 (GPx1), a selenium-dependent enzyme, is associated with lower enzyme activity; however, the evidence is limited to in vitro and observational studies.

OBJECTIVE

The objective was to determine whether the GPx1 Pro200Leu genetic variants modify the response of whole-blood glutathione peroxidase (GPx) activity to selenium supplementation in patients with coronary artery disease in New Zealand.

DESIGN

The results from 2 parallel-design, double-blind trials were combined. Participants were randomly assigned to receive a daily supplement of 100 μg Se as l-selenomethionine (n = 129) or placebo (n = 126) for 12 wk. Plasma selenium and whole-blood GPx activity were measured at baseline and at week 12. Participants were genotyped for the GPx1 Pro200Leu polymorphism.

RESULTS

Selenium supplementation increased whole-blood GPx activity by 5 (95% CI: 4, 7) U/g hemoglobin (P < 0.001); however, the magnitude of the increase did not differ by genotype (P = 0.165 for treatment-by-genotype interaction). In an exploratory analysis, a significant nutrient-gene interaction was apparent when baseline plasma selenium concentrations were included in the regression model (P = 0.006 for treatment-by-genotype × baseline selenium concentration interaction). Increases in GPx activity were 2-fold higher in Pro homozygotes than in participants carrying a Leu allele when baseline selenium concentrations were ≤1.15 μmol/L (P < 0.05).

CONCLUSIONS

These results indicate that GPx1 Pro200Leu variants do not substantially modify the response of whole-blood GPx to selenium supplementation in individuals with relatively high plasma selenium concentrations. A nutrient-gene interaction was observed when the baseline selenium concentration was low, but this requires independent confirmation. This trial was registered at www.actr.org.au as ACTRN12605000412639 and ACTRN12606000197538.

Authors+Show Affiliations

Departments of Human Nutrition, University of Otago, Dunedin, New Zealand. jody.miller@otago.ac.nzNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22952184

Citation

Miller, Jody C., et al. "Influence of the Glutathione Peroxidase 1 Pro200Leu Polymorphism On the Response of Glutathione Peroxidase Activity to Selenium Supplementation: a Randomized Controlled Trial." The American Journal of Clinical Nutrition, vol. 96, no. 4, 2012, pp. 923-31.
Miller JC, Thomson CD, Williams SM, et al. Influence of the glutathione peroxidase 1 Pro200Leu polymorphism on the response of glutathione peroxidase activity to selenium supplementation: a randomized controlled trial. Am J Clin Nutr. 2012;96(4):923-31.
Miller, J. C., Thomson, C. D., Williams, S. M., van Havre, N., Wilkins, G. T., Morison, I. M., Ludgate, J. L., & Skeaff, C. M. (2012). Influence of the glutathione peroxidase 1 Pro200Leu polymorphism on the response of glutathione peroxidase activity to selenium supplementation: a randomized controlled trial. The American Journal of Clinical Nutrition, 96(4), 923-31.
Miller JC, et al. Influence of the Glutathione Peroxidase 1 Pro200Leu Polymorphism On the Response of Glutathione Peroxidase Activity to Selenium Supplementation: a Randomized Controlled Trial. Am J Clin Nutr. 2012;96(4):923-31. PubMed PMID: 22952184.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influence of the glutathione peroxidase 1 Pro200Leu polymorphism on the response of glutathione peroxidase activity to selenium supplementation: a randomized controlled trial. AU - Miller,Jody C, AU - Thomson,Christine D, AU - Williams,Sheila M, AU - van Havre,Nathalie, AU - Wilkins,Gerard T, AU - Morison,Ian M, AU - Ludgate,Jackie L, AU - Skeaff,C Murray, Y1 - 2012/09/05/ PY - 2012/9/7/entrez PY - 2012/9/7/pubmed PY - 2012/12/12/medline SP - 923 EP - 31 JF - The American journal of clinical nutrition JO - Am. J. Clin. Nutr. VL - 96 IS - 4 N2 - BACKGROUND: A genetic variant at codon 200 (Pro200Leu) of the gene encoding for glutathione peroxidase 1 (GPx1), a selenium-dependent enzyme, is associated with lower enzyme activity; however, the evidence is limited to in vitro and observational studies. OBJECTIVE: The objective was to determine whether the GPx1 Pro200Leu genetic variants modify the response of whole-blood glutathione peroxidase (GPx) activity to selenium supplementation in patients with coronary artery disease in New Zealand. DESIGN: The results from 2 parallel-design, double-blind trials were combined. Participants were randomly assigned to receive a daily supplement of 100 μg Se as l-selenomethionine (n = 129) or placebo (n = 126) for 12 wk. Plasma selenium and whole-blood GPx activity were measured at baseline and at week 12. Participants were genotyped for the GPx1 Pro200Leu polymorphism. RESULTS: Selenium supplementation increased whole-blood GPx activity by 5 (95% CI: 4, 7) U/g hemoglobin (P < 0.001); however, the magnitude of the increase did not differ by genotype (P = 0.165 for treatment-by-genotype interaction). In an exploratory analysis, a significant nutrient-gene interaction was apparent when baseline plasma selenium concentrations were included in the regression model (P = 0.006 for treatment-by-genotype × baseline selenium concentration interaction). Increases in GPx activity were 2-fold higher in Pro homozygotes than in participants carrying a Leu allele when baseline selenium concentrations were ≤1.15 μmol/L (P < 0.05). CONCLUSIONS: These results indicate that GPx1 Pro200Leu variants do not substantially modify the response of whole-blood GPx to selenium supplementation in individuals with relatively high plasma selenium concentrations. A nutrient-gene interaction was observed when the baseline selenium concentration was low, but this requires independent confirmation. This trial was registered at www.actr.org.au as ACTRN12605000412639 and ACTRN12606000197538. SN - 1938-3207 UR - https://www.unboundmedicine.com/medline/citation/22952184/Influence_of_the_glutathione_peroxidase_1_Pro200Leu_polymorphism_on_the_response_of_glutathione_peroxidase_activity_to_selenium_supplementation:_a_randomized_controlled_trial_ L2 - https://academic.oup.com/ajcn/article-lookup/doi/10.3945/ajcn.112.043125 DB - PRIME DP - Unbound Medicine ER -