Functional variants in the glutathione peroxidase-1 (GPx-1) gene are associated with increased intima-media thickness of carotid arteries and risk of macrovascular diseases in japanese type 2 diabetic patients
Atherosclerosis in type 2 diabetic patients has been linked to increased oxidative stress. Glutathione peroxidase-1 (GPx-1) plays an important role in the antioxidant defense of the vascular wall. To assess the association between variants in the GPx-1 gene and atherosclerosis, we screened the gene in 184 Japanese type 2 diabetic patients and identified four polymorphisms (-602A/G, +2C/T, Ala(5)/Ala(6), and Pro198Leu). Among these polymorphisms, -602G, +2T, Ala(6), and 198Leu were in strong linkage disequilibrium with each other. The patients were divided into two groups on the basis of the codon 198 polymorphism, Pro/Pro (n = 151) and Pro/Leu (n = 33), to analyze clinical characteristics. The mean intima-media thickness (IMT) of common carotid arteries (P = 0.0028) and the prevalence of cardiovascular disease (P = 0.035) and peripheral vascular disease (P = 0.027) were significantly higher in the Pro/Leu group than in the Pro/Pro group. In vitro functional analyses indicated that the combination of polymorphisms (Ala(6)/198Leu) of the GPx-1 gene had a 40% decrease in enzyme activity, and the combination of polymorphisms (-602G/+2T) had a 25% decrease in transcriptional activity. These results suggest that functional variants in the GPx-1 gene are associated with increased IMT of carotid arteries and risk of cardiovascular and peripheral vascular diseases in type 2 diabetic patients.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2004 |
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| Erschienen: |
2004 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:53 |
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| Enthalten in: |
Diabetes - 53(2004), 9 vom: 28. Sept., Seite 2455-60 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hamanishi, Tohru [VerfasserIn] |
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| Themen: |
EC 1.11.1.9 |
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| Anmerkungen: |
Date Completed 26.10.2004 Date Revised 07.12.2022 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM150101635 |
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| 100 | 1 | |a Hamanishi, Tohru |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Functional variants in the glutathione peroxidase-1 (GPx-1) gene are associated with increased intima-media thickness of carotid arteries and risk of macrovascular diseases in japanese type 2 diabetic patients |
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| 520 | |a Atherosclerosis in type 2 diabetic patients has been linked to increased oxidative stress. Glutathione peroxidase-1 (GPx-1) plays an important role in the antioxidant defense of the vascular wall. To assess the association between variants in the GPx-1 gene and atherosclerosis, we screened the gene in 184 Japanese type 2 diabetic patients and identified four polymorphisms (-602A/G, +2C/T, Ala(5)/Ala(6), and Pro198Leu). Among these polymorphisms, -602G, +2T, Ala(6), and 198Leu were in strong linkage disequilibrium with each other. The patients were divided into two groups on the basis of the codon 198 polymorphism, Pro/Pro (n = 151) and Pro/Leu (n = 33), to analyze clinical characteristics. The mean intima-media thickness (IMT) of common carotid arteries (P = 0.0028) and the prevalence of cardiovascular disease (P = 0.035) and peripheral vascular disease (P = 0.027) were significantly higher in the Pro/Leu group than in the Pro/Pro group. In vitro functional analyses indicated that the combination of polymorphisms (Ala(6)/198Leu) of the GPx-1 gene had a 40% decrease in enzyme activity, and the combination of polymorphisms (-602G/+2T) had a 25% decrease in transcriptional activity. These results suggest that functional variants in the GPx-1 gene are associated with increased IMT of carotid arteries and risk of cardiovascular and peripheral vascular diseases in type 2 diabetic patients | ||
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| 700 | 1 | |a Furuta, Hiroto |e verfasserin |4 aut | |
| 700 | 1 | |a Kato, Hisako |e verfasserin |4 aut | |
| 700 | 1 | |a Doi, Asako |e verfasserin |4 aut | |
| 700 | 1 | |a Tamai, Masanori |e verfasserin |4 aut | |
| 700 | 1 | |a Shimomura, Hiroko |e verfasserin |4 aut | |
| 700 | 1 | |a Sakagashira, Setsuya |e verfasserin |4 aut | |
| 700 | 1 | |a Nishi, Masahiro |e verfasserin |4 aut | |
| 700 | 1 | |a Sasaki, Hideyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Sanke, Tokio |e verfasserin |4 aut | |
| 700 | 1 | |a Nanjo, Kishio |e verfasserin |4 aut | |
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