130 Atherosclerosis Supplements 12, no. 1 (2011) 13–184 Poster presentations the recurrence of atherothrombosis after surgery was evaluated in 107 patients during a 15 years follow up. A significant increased risk was observed only in patients bearing factor II and V homozigous mutations and exposed to cigarette smoke. In the third study 30 subjects underwent SNPs microarray analyses evaluating 197 SNPs for 11 genes involved in atherothrombosis including factor II and V, MTHFR, Antithrombin III, Protein S, Protein C endothelial receptor, Glycoprotein IIa and IIIa, FXII, FXIII, and fibrinogen. No single gene polymorphism was significantly associated with the risk of atherothrombosis. Conversely, the analysis of the whole 197 SNPs profile was able to identify the 6 subjects undergoing recurrences of atherothrombosis. In conclusion, obtained results provide evidence that multiple-SNPs analysis is a better tool for predicting atherothrombosis than single-gene analysis. 616 RISK IMPACT OF 12 PRIOR GWAS CANDIDATE GENES/LOCI FOR CORONARY ARTERY DISEASES IN THE GENETIC ISOLATED NEWFOUNDLAND AND LABRADOR POPULATION Y.-G. Xie 1,2,3,4 , J. Cui 1 , E. Randell 1 , J. Renouf 5 , S. Li 2 , A. Pope 6 , S. Sun 3 , W. Gulliver 3 , B. Sussex 3 , F.-Y. Han 1 . 1 Discipline of Laboratory Medicine, 2 Discipline of Genetics, 3 Discipline of Medicine, 4 Discipline of Pediatrics, Memorial University of Newfoundland, 5 Laboratory Medicine Program, Eastern Health, 6 Deptment of Molecular Genetics, Newfound Genomics, St. John’s, NL, Canada Genome-wide association studies (GWAS), have provided some promising achievements for a number of multifactor diseases including coronary artery disease (CAD). However, many of these GWAS candidate genes failed to been replicated in studies using different ethnic populations which indicates the variety of genetic modifiers among ethnic populations. Additionally, the genetic heterogeneity in the studied population can reduce the sensitivity in detection of weak genetic effects and leads to false negative results in replication studies. The population of Newfoundland and Labrador (NL) is a well known genetic isolated population, and this population has a high prevalence of CAD in Canada. As a part of our ongoing study, 15 genetic variants from 12 selected prior GWAS candidate genes/loci have been genotyped in 500 patients with myocardial infarction (MI) and 500 sex controls from the NL population to determine the disease risk impact in the studied population. Genotyping was carried out by using the Sequenom’s MassARRAY ® system. Among the 12 studied genes/loci, only the 9p21 locus (rs 133049, rs 10757274, rs238306 and rs238307) was successfully associated to the patients (P < 0.000 in all SNPs). This association was further confirmed in another study with enlarged sample size (1,000 MI patients and 1,000 controls) from the same population (P < 0.000 in all SNPs). We, therefore, conclude that the 9p21 locus is a genetic susceptibility for CAD in the NL population. The failure of replicating other11 GWAS candidate genes for CAD in NL patients strongly suggests the diversity of genetic modifiers for CAD in NL population. 617 DAXX AS A NOVEL TARGET IN THE PREVENTION OF ATHEROSCLEROSIS D. Liao 1 , Q. Tuo 2 , G. Xu 2 , B. Su 2 , Q. He 2 , B. Zhu 2 . 1 Department of Traditional Chinese Diagnotics, Hunan University of Chinese Medicine, Changsha, 2 Institute of Pharmacy and Pharmacology, University of South China, Hengyang, China Daxx was initially identified as a pro-apoptotic protein that binds to the Fas death domain, and plays a crucial role in the cellular apoptosis response to UV, oxidative stress, and et al. Oxidized low-density lipoprotein (ox-LDL) is an important sources of oxidative stress and can induce macrophage apoptosis. We found that ox-LDL increased apoptosis and Daxx expression of THP-1 cell in a time- and dose-dependent manner, and facilitated Daxx translocation from cytoplasm to nucleus. Antioxidant probucol (50 mol/L) for 4 hr prior to exposure to ox-LDL significantly inhibited Daxx expression and THP-1 macrophage apoptosis, which was related to regulation of caspase-3 expression. Furthermore, ox-LDL-induced macrophage apoptosis were accompanied by intercellular cholesterol accumulation and expression of caveolin-1 in RAW264.7. The later is associated with selective cholesterol ether uptake and cellular apoptosis in macrophages. As expected, siRNA-Daxx inhibited ox-LDL effects on macrophages. Some evidence implied Daxx can inhibit androgen receptor transcriptional activity, which can down-regulates the activity of sterol regulatory element- binding protein (SREBP), an inhibiting protein of caveolin gene transcription. Overexpression of Daxx in HepG 2 cells decreased intracellular cholesterol accumulation, increased caveolin-1 expression, as well as inhibitted SREBP activity. The functional domain of Daxx (aa626–740) can combine with androgen recepter by GST pull-down and decrease cellular cholesterol contents when transfed into HepG 2 cells. In conclusion, Daxx mediated ox-LDL-induced apoptosis, cholesterol accumulation in macrophage by regulating expression of caspase-3 and caveolin-1, and by inhibiting activity of SREBP. Daxx may be considered as a novel target in the prevention of atherosclerosis. This work was supported by grants from the National Natural Science Foundation of China (3097117, 30600249, 30971267) 618 KV1.5 MODULATES OXLDL-INDUCED ENDOTHELIAL INJURY VIA MITOCHONDRIAL ROS G.-L. Wang, Y.-Y. Guan, W.-L. Chen. Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China Background and Aims: Kv1.5 channel activity in excitable cells can be modified by reactive oxygen species (ROS), and thus have been highlighted in association with the pathophysiological processes of pulmonary arterial hypertension and some cancers. Here we have addressed the question whether modulation of Kv 1.5 channel expression contributes to an in vitro oxLDL-induced oxidative injury model in endothelial cells via mitochondrial ROS. Material and Methods: To examine the role of Kv1.5 in oxLDL induced endothelial injury, we used adenovirus vector overexpressing of Kv1.5 and siRNA-mediated knockdown of Kv1.5 to analyze the change in ROS production, mitochondrial function and oxidative injury induced by oxLDL in human pulmonary arterial endothelial cells (HPAECs). Results: Incubation with 150 mg/ml oxLDL for 24h induced significant cell injury, evidenced by DAPI staining and inverted microscopy observation. OxLDL also enhanced Kv1.5 expression in a concentration-dependent manner. This correlated with enhanced levels of intracellular ROS and mitocondria-derived ROS. Overexpression of Kv1.5 increased oxLDL-induced cellular damage, intracellular or mitochondria-derived ROS. In contrast, the induction of oxidative cell damage and excess ROS generation were significantly attenuated by Kv1.5 siRNA interference or Kv1.5 inhibitor. The siRNA and adnoviral assays also showed that mitochondria uncoupling protein 2 (UCP2) was involved in the modulation of oxLDL-induced endothelial damage by Kv1.5. Conclusion: These findings suggest that Kv1.5 plays a crucial role in the regulation of oxLDL-induced endothelial injury through mitochondrial-derived ROS generation, making it a promising target for treatment of atherosclerosis. 619 GENETIC VARIANTS ASSOCIATED WITH PRIMARY HYPERTRIGLYCERIDEMIA M. Solanas-Barca 1 , E. Jarauta 1 , P. Mart´ ın-Fuentes 1 , M. Cof´ an 2 , E. Ros 2 , L. Masana 3 , N. Plana 3 , A. Cenarro 1 , F. Civeira 1 . 1 Unidad de L´ ıpidos and Laboratorio de Investigaci´ on Molecular, Hospital Universitario Miguel Servet. I+CS, Zaragoza, 2 Unidad de L´ ıpidos, Hospital Cl´ ınic de Barcelona, Barcelona, 3 Unidad de Riesgo Vascular, Hospital San Joan, Reus, Spain Introduction: Most primary hypertriglyceridemias are caused by the interaction of genetic and environmental factors. The identification of this genetic component may contribute to improving their diagnosis and treatment. Studies have shown that the genetic background of hypertriglyceridemia is highly heterogeneous, as both rare variants with large effects and common variants with moderate effects have been described. However, the additive effects of all these genetics variants have not been explored in a large hypertriglyceridemic cohort. Objective: To identify genetic loci associated with primary hypertriglyceridemia and the additive effect of the variants identified. Methods: Case-control study of 42 polymorphisms in 33 different loci previously associated with plasma triglyceride concentrations. We genotyped these polymorphisms in 1100 subjects, 453 controls and 647 unrelated patients with primary hypertriglyceridemia from 3 lipid clinics in Spain. 36 polymorphisms were analysed by Maldi-Tof mass spectrometry and the other 6 by PCR- sequencing or TaqMan assays. Results: A significantly different between-group allelic frequency was found for APOE, LPL, APOA5, CYP7A1, GCKR, ANGPTL3, TRIB1, and TCF7L2 variants. Genotype distribution showed significant differences for APOE, LPL, APOA5, GCKR, ANGPTL3, TRIB1, AIPOR2, GALNT2, FADS3, and HFE. Only the homozygous minor allele frequency distribution was significantly different between groups for GALNT2 FADS3, ANGPTL3, GALNT2 and HFE polymorphisms, indicating that a double dose of the minor allele was associated with hypertriglyceridemia. Additive effects on hypertriglyceridemia were found for APOE, APOA5 and GCKR variant associations. Conclusion: We identified several genetic variants associated with primary hy- pertriglyceridemia. The contribution of these variants is highly heterogeneous. 620 A POLYMORPHISM IN THE HEART SPECIFIC FATTY ACID TRANSPORT PROTEIN 6 IS ASSOCIATED WITH THE METABOLIC SYNDROME AND CARDIOVASCULAR DISEASE A. Auinger 1 , U. Helwig 2 , D. Rubin 2 , M. de Vrese 1 , M. L¨ udde 3 , T. Rausche 3 , N. Elmoktari 3 , N. Frey 3 , J. Schrezenmeir 4 . 1 Department of Microbiology and Biotechnology, Max Rubner-Institute, 2 University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Clinic for General Internal Medicine, 3 University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Department of Cardiology, Kiel, 4 Department of Physiology and Biochemistry of Nutrition, Max Rubner-Institute, Karlsruhe, Germany Introduction: The fatty acid transport protein 6 (FATP6) is primarily expressed in the heart and seems to be involved in the cardiac fatty acids uptake. Therefore we investigated whether a variation in the 5 ′ untranslated region (UTR) of the