Association of OAZ1 gene polymorphisms with subclinical and clinical vascular events
OBJECTIVE: Proliferation and migration of vascular smooth muscle cells (VSMCs) are striking features shared by vascular ageing, atherosclerosis, and in-stent restenosis. VSMC biology depends in part on polyamines whose metabolism is closely regulated by ornithine decarboxylase antizyme 1 (OAZ1). Therefore, we sought for association between OAZ1 gene polymorphisms and various outcomes involving VSMC proliferation.
METHODS AND RESULTS: Systematic screening of the OAZ1 gene enabled to detect 21 variants. The impact of 4 selected tag polymorphisms (+849C/T, +851G/T, +1804G/A, and +2222A/G) was evaluated in 3 independent association studies. In a sample of 205 patients, the +2222G allele was associated with an increased risk of 6-month coronary in-stent restenosis (OR [95%CI]=2.1 [1.2 to 3.6]; P=0.0071). In a sample of 1001 subjects participating to the EVA study, the +2222G allele was longitudinally associated with a 4-year increase in common carotid intima-media thickness (P=0.047). In a case-control study (466 cases versus 466 controls), the risk of coronary heart disease associated with the +2222G allele was 1.3 (95%CI=[1.1 to 1.6]; P=0.026). No other significant association was consistently detected.
CONCLUSIONS: We identified the OAZ1+2222A/G polymorphism as a potential genetic marker of vascular events. Our findings strengthen the hypothesis that the polyamine metabolism plays a role in vascular diseases.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2007 |
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| Erschienen: |
2007 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
|---|---|
| Enthalten in: |
Arteriosclerosis, thrombosis, and vascular biology - 27(2007), 10 vom: 31. Okt., Seite 2120-6 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Dumont, Julie [VerfasserIn] |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 11.10.2007 Date Revised 20.09.2007 published: Print-Electronic Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
|
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| PPN (Katalog-ID): |
NLM172731666 |
|---|
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| 100 | 1 | |a Dumont, Julie |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Association of OAZ1 gene polymorphisms with subclinical and clinical vascular events |
| 264 | 1 | |c 2007 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 11.10.2007 | ||
| 500 | |a Date Revised 20.09.2007 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: Proliferation and migration of vascular smooth muscle cells (VSMCs) are striking features shared by vascular ageing, atherosclerosis, and in-stent restenosis. VSMC biology depends in part on polyamines whose metabolism is closely regulated by ornithine decarboxylase antizyme 1 (OAZ1). Therefore, we sought for association between OAZ1 gene polymorphisms and various outcomes involving VSMC proliferation | ||
| 520 | |a METHODS AND RESULTS: Systematic screening of the OAZ1 gene enabled to detect 21 variants. The impact of 4 selected tag polymorphisms (+849C/T, +851G/T, +1804G/A, and +2222A/G) was evaluated in 3 independent association studies. In a sample of 205 patients, the +2222G allele was associated with an increased risk of 6-month coronary in-stent restenosis (OR [95%CI]=2.1 [1.2 to 3.6]; P=0.0071). In a sample of 1001 subjects participating to the EVA study, the +2222G allele was longitudinally associated with a 4-year increase in common carotid intima-media thickness (P=0.047). In a case-control study (466 cases versus 466 controls), the risk of coronary heart disease associated with the +2222G allele was 1.3 (95%CI=[1.1 to 1.6]; P=0.026). No other significant association was consistently detected | ||
| 520 | |a CONCLUSIONS: We identified the OAZ1+2222A/G polymorphism as a potential genetic marker of vascular events. Our findings strengthen the hypothesis that the polyamine metabolism plays a role in vascular diseases | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Polyamines |2 NLM | |
| 650 | 7 | |a Proteins |2 NLM | |
| 650 | 7 | |a ornithine decarboxylase antizyme |2 NLM | |
| 700 | 1 | |a Zureik, Mahmoud |e verfasserin |4 aut | |
| 700 | 1 | |a Bauters, Christophe |e verfasserin |4 aut | |
| 700 | 1 | |a Grupposo, Marie-Catherine |e verfasserin |4 aut | |
| 700 | 1 | |a Cottel, Dominique |e verfasserin |4 aut | |
| 700 | 1 | |a Montaye, Michèle |e verfasserin |4 aut | |
| 700 | 1 | |a Hamon, Martial |e verfasserin |4 aut | |
| 700 | 1 | |a Ducimetière, Pierre |e verfasserin |4 aut | |
| 700 | 1 | |a Amouyel, Philippe |e verfasserin |4 aut | |
| 700 | 1 | |a Brousseau, Thierry |e verfasserin |4 aut | |
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