Arteriosclerosis, thrombosis, and vascular biology · 2007
Association of OAZ1 gene polymorphisms with subclinical and clinical vascular events.
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Dumont Julie, Zureik Mahmoud, Bauters Christophe, Grupposo Marie-Catherine, Cottel Dominique, Montaye Michèle, Hamon Martial, Ducimetière Pierre, Amouyel Philippe, Brousseau Thierry
Аннотация
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.
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.
Предметные рубрики MeSH
AgedCardiovascular DiseasesCarotid Artery DiseasesCase-Control StudiesCell ProliferationCoronary DiseaseCoronary RestenosisFemaleGene FrequencyGenetic Predisposition to DiseaseHumansLinkage DisequilibriumLongitudinal StudiesMaleMiddle AgedMuscle, Smooth, VascularMyocytes, Smooth MuscleOdds RatioPhenotypePolyaminesPolymorphism, Single NucleotideProteinsRisk AssessmentRisk Factors