A Novel Single Nucleotide Polymorphism in the 3′ Untranslated Region of Human Glutathione Peroxidase 4 Influences Lipoxygenase Metabolism

Villette, Stephane; Kyle, James; Brown, Katrina; Pickard, Karen; Milne, John; Nicol, Fergus; Arthur, John R.; Hesketh, John E.

doi:10.1006/bcmd.2002.0556

Cited by 96 publications

(98 citation statements)

References 15 publications

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“…Furthermore, in vivo the association between GPx1 activity and Se concentration differed between groups of different genotype suggesting that this SNP modifies the response of GPx1 activity to Se (24) The Leucine variant is relatively rare, the homozygous allele being found in only 7-11% of Caucasians and about 15 % of Afro-Caribbeans. Sequencing of the 3 0 -UTR region of the GPX4 gene led to the identification of an SNP (T/C variant: rs713041) in Caucasians in a UK population (25) . Subsequently, this SNP has been found in other ethnic groups (16,26) .…”

Section: Functional Single-nucleotide Polymorphisms Inmentioning

confidence: 99%

Transcriptomics and functional genetic polymorphisms as biomarkers of micronutrient function: focus on selenium as an exemplar

Hesketh

Méplan

2011

Proc. Nutr. Soc.

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Micronutrients are essential for optimal human health. However, in some cases, raising intake by supplementation has not proven to be beneficial and there is even some evidence that supplementation may increase disease risk, highlighting the importance of assessing the functional status of micronutrients. Techniques such as gene microarrays and single-nucleotide polymorphism analysis have the potential to examine effects of micronutrient intake on patterns of gene expression and inter-individual variation in micronutrient metabolism. Recent genomic research related to selenium (Se) provides examples illustrating how studies of functional single-nucleotide polymorphism and gene expression patterns can reveal novel biomarkers of micronutrient function. Both in vitro and in vivo experiments show that there are functionally relevant polymorphisms in genes encoding glutathione peroxidases 1, 3 and 4, selenoprotein P, selenoprotein S and the 15 kDa selenoprotein. Disease association studies investigating these gene variants have so far been relatively small but an association of a polymorphism in the selenoprotein S gene with colorectal cancer risk has been replicated in two distinct populations. Future disease association studies should examine effects of multiple variants in combination with nutritional status. Gene microarray studies indicate that changes in Se intake alter expression of components of inflammatory, stress response and translation pathways. Our hypothesis is that Se intake and genetic factors have linked effects on stress response, inflammation and apoptotic pathways. Combining such data in a systems biology approach has the potential to identify both biomarkers of micronutrients status and sub-group populations at particular risk.

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Section: Functional Single-nucleotide Polymorphisms Inmentioning

confidence: 99%

Transcriptomics and functional genetic polymorphisms as biomarkers of micronutrient function: focus on selenium as an exemplar

Hesketh

Méplan

2011

Proc. Nutr. Soc.

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“…15 The gene for glutathione peroxidase-4 is expressed in most tissues, including the brain (Gene Expression Atlas, available at http://www.ebi.ac.uk/gxa/gene/ ENSG00000167468). Although the GPX4 gene is highly polymorphic, a limited number of studies [16][17][18][19] have been done to investigate genetic variations within the GPX4 gene that could potentially alter the function of the enzyme. There is a C-to-T single-nucleotide polymorphism at the 718 position (rs713041) located in the 3¢-untranslated region of the GPX4 gene close to the predicted selenocysteine insertion sequence structure (SECIS, a region of the mRNA required for incorporation of the amino acid Sec into GPX4).…”

Section: Biological Role and Functional Studies Of The Gpx4 Genementioning

confidence: 99%

“…There is a C-to-T single-nucleotide polymorphism at the 718 position (rs713041) located in the 3¢-untranslated region of the GPX4 gene close to the predicted selenocysteine insertion sequence structure (SECIS, a region of the mRNA required for incorporation of the amino acid Sec into GPX4). 17 This polymorphism is involved in the modulation of the GPX4 synthesis by altering the affinity of the selenocysteine insertion machinery for its SECIS element. 20 Bermano and coworkers 19 have observed that the C variant at the 3¢-untranslated region of the GPX4 gene was stronger than the T variant at driving biosynthesis of a selenoprotein reporter.…”

Section: Biological Role and Functional Studies Of The Gpx4 Genementioning

confidence: 99%

“…Notably, the 718C allele of the GPX4 gene was found to be associated with the increased levels of lymphocyte lipoxygenase products implying that The GPX4 gene and stroke-complicated hypertension AV Polonikov et al the polymorphism can modulate inflammatory processes through the regulation of the biosynthesis of leukotrienes, thromboxanes and prostaglandins. 17 It has been revealed that the inflammation has an important role in the pathogenesis of CS, and various inflammatory markers have been investigated as predictors of the disease. 26 Therefore, we suggest that hypertensive individuals with the 718C variant of the GPX4 gene are susceptible to CS because of the increased concentration or activity of the enzyme promoting proinflammatory processes and increasing the brain injury.…”

Section: Biological Role and Functional Studies Of The Gpx4 Genementioning

confidence: 99%

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The C718T polymorphism in the 3′-untranslated region of glutathione peroxidase-4 gene is a predictor of cerebral stroke in patients with essential hypertension

et al. 2011

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In the present study we have investigated the association of three single nucleotide polymorphisms in glutathione peroxidase (GPx) genes GPX1 rs1050450 (P198L), GPX3 rs2070593 (G930A) and GPX4 rs713041 (T718C) with the risk of cerebral stroke (CS) in patients with essential hypertension (EH). A total of 667 unrelated EH patients of Russian origin, including 306 hypertensives (the EH-CS group) who suffered from CS and 361 people (the EH-CS group) who did not have cerebrovascular accidents, were enrolled in the study. The variant allele 718C of the GPX4 gene was found to be significantly associated with an increased risk of CS in hypertensive patients (odds ratio (OR) 1.53, 95% confidence interval (CI) 1.23-1.90, P adj ¼0.0003). The prevalence of the 718TC and 718CC genotypes of the GPX4 gene was higher in the EH-CS group than the EH-alone group (OR¼2.12, 95%CI 1.42-3.16, P adj ¼0.0018). The association of the variant GPX4 genotypes with the increased risk of CS in hypertensives remained statistically significant after adjusting for confounding variables such as sex, body mass index (BMI), blood pressure and antihypertensive medication use (OR¼2.18, 95%CI 1.46-3.27, P¼0.0015). Multiple logistic regression analysis did not reveal any interaction between various combinations of GPX1, GPX3 and GPX4 genotypes regarding the risk of CS in patients with EH. The study demonstrated for the first time that the C718T polymorphism in the 3¢-untranslated region of the GPX4 gene could be considered as a genetic marker of susceptibility to CS in patients with EH.

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“…The lack of difference in expression across genotypes may have been due to the small sample size of the specimens (37 lymphocytes, five normal breast and 13 tumors) and warrants further investigation. Furthermore, one of these SNPs, rs713041, has previously been reported to be associated with levels of 5-lipoxygenase metabolites [7].…”

Section: Germline Genetics and Disease Outcomementioning

confidence: 99%

Germline Genetic Variation and Breast Cancer Survival: Prognostic and Therapeutic Implications

Udler

Pharoah

2007

Future Oncol.

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A Novel Single Nucleotide Polymorphism in the 3′ Untranslated Region of Human Glutathione Peroxidase 4 Influences Lipoxygenase Metabolism

Cited by 96 publications

References 15 publications

Transcriptomics and functional genetic polymorphisms as biomarkers of micronutrient function: focus on selenium as an exemplar

Transcriptomics and functional genetic polymorphisms as biomarkers of micronutrient function: focus on selenium as an exemplar

The C718T polymorphism in the 3′-untranslated region of glutathione peroxidase-4 gene is a predictor of cerebral stroke in patients with essential hypertension

Germline Genetic Variation and Breast Cancer Survival: Prognostic and Therapeutic Implications

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