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632 HIGH FREQUENCY OF NPY POLYMORPHISM IN IRAN AND ITS ASSOCIATION WITH CORONARY ARTERY DISEASE
79th EAS Congress
Atherosclerosis Supplements 12, no. 1 (2011) 13–184
evident for HDL-cholesterol concentration when patients were treated with nonnucleoside reverse transcriptase inhibitors (1.05±0.4 vs. 1.28±0.4 mmol/L). Conclusions: The A allelic variant of the rs10892151 polymorphism is not associated with serum apo C-III concentration, but predisposes HIV-infected patients to less favorable lipid profile, particularly in those patients treated with PIs. 630 PHARMACOGENETICS OF STATIN TREATMENT EFFICACY: ANALYSIS OF GENETIC VARIATION AT EIGHT CANDIDATE GENE LOCI M. Vrablik1 , J. Hubacek2 , V. Adamkova2 , M. Prusikova1 , L. Zlatohlavek1 , V. Lanska2 , R. Ceska1 . 1 3rd Dept. of Internal Medicine, Charles University, Medical Faculty and Faculty Hospital, 2 Institute for Clinical and Experimental Medicine, Prague, Czech Republic Introduction: Statins are drugs of choice in patients with increased cardiovascular risk. A significant inter-individual variability in statin treatment efficacy has a genetic background. Several candidate genes and gene regions have been shown to impact on therapeutic response to statins. Methods: Ten variants in eight genes/gene regions (CELSR2/PSRC1/SORT1, CILP2/PBX4, APOB, APOE/C1/C4, HMG-CoA-R, LDL receptor, PCSK9) were analyzed in 771 (40% males; average age 59.5 years) patients with dyslipidemia treated with equipotent doses of statins (39% simvastatin, 45% atorvastatin). Genotype frequencies were compared to 470 normolipidemic controls (188 males). rs599838, rs646776, rs16996148, rs693, rs515135, rs4420638, rs12654264, rs6511720, rs11591147 a rs11206510 polymorphisms were determined using PCR and restriction analysis. Lipid levels were available prior to the treatment and after 8−12 weeks of therapy. Results: Genotype frequencies of all analysed SNPs (except for one in APOB and one in PCSK9 genes) were different between patients and controls (all p-values between 0.05 and 0.005). rs646776 variant in CELS/PSRC1/SORT1 region was not detected in studied Czech population. There was no significant association detected neither between individual SNPs, nor in subgroups defined by combinations of different alleles and statin treatment efficacy. No difference in statin treatment efficacy was observed between groups defined according the numbers of cholesterol increasing alleles. Conclusion: Our study demonstrated that, although associated with plasma TC and LDL cholesterol per se, variants within CELSR2/PSRC1/SORT1, CILP2/PBX4, APOB, APOE/C1/C4, HMG-CoA-R, LDL receptor and PCSK9 genes are not modifiers of response to statin treatment. Supported by project No. NS 10579−3 from the IGA, MH, Czech Republic. 631 DIFFERENTIAL PERIPHERAL-BLOOD GENE EXPRESSION IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION AND STABLE CORONARY DISEASE S. Nahum1 , Y. Drier2 , N. Avidan3 , E. Domani4 , E. Sprecher1 , D. Aronson3 . 1 Technion, 2 Weizmann Inst of Science, 3 Technion Faculty of Medicine, Haifa, 4 Weizmann Inst of Science, Rehovot, Israel Background: Recent studies have shown that patients with angiographically defined coronary artery disease (CAD) may be distinguished from subjects without CAD by gene expression analysis of peripheral-blood cells. However, there is no data with regard to differential blood cell gene expression in the context of coronary plaque rupture and stable coronary disease. Methods: In a prospective, case control study we identified 28 patients with CAD. Cases (n = 14) included patients >3 months after an acute STelevation myocardial infarction (STEMI) and angiographic evidence of 1-vessel disease with plaque rupture. The control group (n = 14) included patients with angiographic evidence of multivessel CAD (70% stenosis in 2 vessels) but without clinical, electrocardiographic or echocardiographic evidence of prior infarction. Results: Whole genome microarray analysis of performed on peripheral-blood mononuclear cells (Illumina Human-6 BeadChip) disclosed 16 genes with >1.3fold differential expression (P < 0.05). The most differentially upregulated genes in the multivessel CAD group included interleukin-1b (2.5-fold, P < 0.001), transcription factor early growth response-1 and 2 (2.2−2.7-fold, P < 0.001) and cyclooxygenase-2 (3.5-fold, P < 0.01). Real-time PCR confirmed increased expression of these transcripts. Ingenuity pathway analysis revealed that networks involved in inflammation and cell growth (including regulation of NFúB) exhibited highest z scores, reflecting higher cellular inflammatory activation in multivessel CAD. Conclusions: Gene expression in peripheral-blood cells identified differential expression patterns in two distinct subgroups of patients with different manifestations of CAD. Increased expression of inflammatory genes is associated with the burden atheroma rather than with a plaque rupture and myocardial infarction.
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632 HIGH FREQUENCY OF NPY POLYMORPHISM IN IRAN AND ITS ASSOCIATION WITH CORONARY ARTERY DISEASE A.M. Kazemabad1 , M. Ghayour Mobarhan2 , K. Jamialahmadi2 , M. Moohebati3 , M. Mojarrad4 , R. Dehghan manshadi2 , M.M. Forghanifard5 . 1 Department of Biology, Islamic Azad University, Sciences and Research Branch, Tehran, 2 Department of Biochemistry and Nutrition, Mashhad University of Medical Sciences, 3 Department of Cardiology, Ghaem Hospital, Mashad University of Medical Sciences, 4 Department of Genetic, Mashhad University of Medical Sciences, Mashhad, 5 Department of Biology, Islamic Azad University, Damghan Branch, Damghan, Iran Objectives: Neuropeptide Y (NPY) is a protein with variable expression in different tissues especially in the heart, central and peripheral nerves systems. There is a relationship between NPY gene variants and coronary artery disease (CAD) in some population. However, there is a little data about NPY gene polymorphism and CAD in Iran. Therefore, we investigated the relationship between NPY gene 1128T>C and the outbreak of CAD in Iran. Methods: A total of 1061 subjected were recruited; 609 patients and 452 healthy subjects. Among 609 patients, 428 patients had more than 50% stenosis and 181 patients had less than 50% stenosis based on angiography. Angiogheraphy positive patients were divided into single vessel (n = 115), two vessels (n = 140), and three vessels (n = 173). Samples DNA was extracted in salting out method and the 1128T>C polymorphism and PCR-RFLP technique were recognized for all subjects. Results: A significant increasing in C allele and TC genotype frequency were observed in all patients compared with the control group (p < 0.05). Also, some subgroups of our subjects such as obese vs. non obese subjects and dyslipidemia vs. non dyslidpideamia had significantly higher TC genotype (p < 0.01). However, there were not significant differences among subgroups; metabolic syndrome vs. non-metabolic syndrome, hypertensive vs. nonhypertensive, diabetes vs. non-diabetes between polymorphism of NPY. The frequency of Pro7 substitution was 5.9% in our population. Conclusion: The frequency of T1128C polymorphism of NPY was 6% in Iranian population, which is higher than other Asian population. This polymorphism was associated with CAD in Iranian population. 633 AHSG GENE POLYMORPHISM AFFECTS PLASMA LEVELS OF NONHIGH-DENSITY LIPOPROTEIN CHOLESTEROL IN CAUCASIANS P. Suchanek, J.A. Hubacek, I. Kralova Lesna, V. Adamkova. Cardiovascular Research Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic Introduction: To evaluate the relationship between AHSG gene and plasma lipid levels. The alpha2 Heremans-Schmid glycoprotein (AHSG) gene is implicated in the regulation of body fat and insulin sensitivity. The genotype Met/Met (SNP rs4917) was associated with a marked increase in the lipolytic sensitivity to beta2-adrenoreceptor adipocyte on contrary to Thr carriers. We have evaluated the influence of common AHSG gene polymorphism (Thr248Met) on plasma lipid concentrations in 1% representative sample of the Czech population aged 25−65 years. Aim: The influence of Thr248Met polymorphisms in the AHSG gene on plasma cholesterol fractions was evaluated in 1152 men and 1345 women from the Czech population. Total, low-density lipoprotein cholesterol and HDL cholesterol levels were analyzed. Results: The Thr/Met variation in the AHSG gene was found to affect plasma on total and LDL cholesterol, showing significantly higher levels in Thr/Thr carriers than in Met/Met homozygotes. This association was observed in both men (TC 5.76±1.03 mmol/L in Thr/Thr carriers versus 5.48±0.90 mmol/L in Met/Met homozygotes; P < 0.001; LDL cholesterol 3.67±0.88 mmol/L in Thr/Thr carriers versus 3.40±0.77 mmol/L in Met/Met homozygotes; P < 0.01) and women (TC 5.77±1.17 mmol/L in Thr/Thr carriers versus 5.56±0.97 mmol/L in Met/Met homozygotes; P < 0.001; LDL cholesterol 3.63±1.05 mmol/L in Thr/Thr carriers versus 3.46±0.91 mmol/L in Met/Met homozygotes; P < 0.01). Conclusion: AHSG gene polymorphism plays a role in the genetic determination of total cholesterol and LDL cholesterol levels. This project was supported by grant NS 10513−3/2009 from the Internal Grant Agency of the Ministry of Health of the Czech Republic. 634 GENDER DEPENDENT ASSOCIATION BETWEEN KIF6 POLYMORPHISM AND RISK OF UNFAVORABLE OUTCOME IN PATIENTS SURVIVED ACUTE CORONARY SYNDROME O.S. Koroleva1 , M.A. Evdokimova1 , A.A. Pushkov2 , K.A. Blagodatskich2 , V.V. Nosikov2 , D.A. Zateyshchikov1 . 1 FSI Educational Scientific Medical Centre” of the General Management Department of the President of Russian Federation, 2 National Research Centre “GosNII Genetika”, Moscow, Russia Objectives: It is obvious that individual genetic features play important role in the unfavourable outcomes (UO) after acute coronary syndrome (ACS). We have studied association between polymorphism of KIF6 gene and risk of UO in patients after ACS.
Atherosclerosis Supplements 12, no. 1 (2011) 13–184
evident for HDL-cholesterol concentration when patients were treated with nonnucleoside reverse transcriptase inhibitors (1.05±0.4 vs. 1.28±0.4 mmol/L). Conclusions: The A allelic variant of the rs10892151 polymorphism is not associated with serum apo C-III concentration, but predisposes HIV-infected patients to less favorable lipid profile, particularly in those patients treated with PIs. 630 PHARMACOGENETICS OF STATIN TREATMENT EFFICACY: ANALYSIS OF GENETIC VARIATION AT EIGHT CANDIDATE GENE LOCI M. Vrablik1 , J. Hubacek2 , V. Adamkova2 , M. Prusikova1 , L. Zlatohlavek1 , V. Lanska2 , R. Ceska1 . 1 3rd Dept. of Internal Medicine, Charles University, Medical Faculty and Faculty Hospital, 2 Institute for Clinical and Experimental Medicine, Prague, Czech Republic Introduction: Statins are drugs of choice in patients with increased cardiovascular risk. A significant inter-individual variability in statin treatment efficacy has a genetic background. Several candidate genes and gene regions have been shown to impact on therapeutic response to statins. Methods: Ten variants in eight genes/gene regions (CELSR2/PSRC1/SORT1, CILP2/PBX4, APOB, APOE/C1/C4, HMG-CoA-R, LDL receptor, PCSK9) were analyzed in 771 (40% males; average age 59.5 years) patients with dyslipidemia treated with equipotent doses of statins (39% simvastatin, 45% atorvastatin). Genotype frequencies were compared to 470 normolipidemic controls (188 males). rs599838, rs646776, rs16996148, rs693, rs515135, rs4420638, rs12654264, rs6511720, rs11591147 a rs11206510 polymorphisms were determined using PCR and restriction analysis. Lipid levels were available prior to the treatment and after 8−12 weeks of therapy. Results: Genotype frequencies of all analysed SNPs (except for one in APOB and one in PCSK9 genes) were different between patients and controls (all p-values between 0.05 and 0.005). rs646776 variant in CELS/PSRC1/SORT1 region was not detected in studied Czech population. There was no significant association detected neither between individual SNPs, nor in subgroups defined by combinations of different alleles and statin treatment efficacy. No difference in statin treatment efficacy was observed between groups defined according the numbers of cholesterol increasing alleles. Conclusion: Our study demonstrated that, although associated with plasma TC and LDL cholesterol per se, variants within CELSR2/PSRC1/SORT1, CILP2/PBX4, APOB, APOE/C1/C4, HMG-CoA-R, LDL receptor and PCSK9 genes are not modifiers of response to statin treatment. Supported by project No. NS 10579−3 from the IGA, MH, Czech Republic. 631 DIFFERENTIAL PERIPHERAL-BLOOD GENE EXPRESSION IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION AND STABLE CORONARY DISEASE S. Nahum1 , Y. Drier2 , N. Avidan3 , E. Domani4 , E. Sprecher1 , D. Aronson3 . 1 Technion, 2 Weizmann Inst of Science, 3 Technion Faculty of Medicine, Haifa, 4 Weizmann Inst of Science, Rehovot, Israel Background: Recent studies have shown that patients with angiographically defined coronary artery disease (CAD) may be distinguished from subjects without CAD by gene expression analysis of peripheral-blood cells. However, there is no data with regard to differential blood cell gene expression in the context of coronary plaque rupture and stable coronary disease. Methods: In a prospective, case control study we identified 28 patients with CAD. Cases (n = 14) included patients >3 months after an acute STelevation myocardial infarction (STEMI) and angiographic evidence of 1-vessel disease with plaque rupture. The control group (n = 14) included patients with angiographic evidence of multivessel CAD (70% stenosis in 2 vessels) but without clinical, electrocardiographic or echocardiographic evidence of prior infarction. Results: Whole genome microarray analysis of performed on peripheral-blood mononuclear cells (Illumina Human-6 BeadChip) disclosed 16 genes with >1.3fold differential expression (P < 0.05). The most differentially upregulated genes in the multivessel CAD group included interleukin-1b (2.5-fold, P < 0.001), transcription factor early growth response-1 and 2 (2.2−2.7-fold, P < 0.001) and cyclooxygenase-2 (3.5-fold, P < 0.01). Real-time PCR confirmed increased expression of these transcripts. Ingenuity pathway analysis revealed that networks involved in inflammation and cell growth (including regulation of NFúB) exhibited highest z scores, reflecting higher cellular inflammatory activation in multivessel CAD. Conclusions: Gene expression in peripheral-blood cells identified differential expression patterns in two distinct subgroups of patients with different manifestations of CAD. Increased expression of inflammatory genes is associated with the burden atheroma rather than with a plaque rupture and myocardial infarction.
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632 HIGH FREQUENCY OF NPY POLYMORPHISM IN IRAN AND ITS ASSOCIATION WITH CORONARY ARTERY DISEASE A.M. Kazemabad1 , M. Ghayour Mobarhan2 , K. Jamialahmadi2 , M. Moohebati3 , M. Mojarrad4 , R. Dehghan manshadi2 , M.M. Forghanifard5 . 1 Department of Biology, Islamic Azad University, Sciences and Research Branch, Tehran, 2 Department of Biochemistry and Nutrition, Mashhad University of Medical Sciences, 3 Department of Cardiology, Ghaem Hospital, Mashad University of Medical Sciences, 4 Department of Genetic, Mashhad University of Medical Sciences, Mashhad, 5 Department of Biology, Islamic Azad University, Damghan Branch, Damghan, Iran Objectives: Neuropeptide Y (NPY) is a protein with variable expression in different tissues especially in the heart, central and peripheral nerves systems. There is a relationship between NPY gene variants and coronary artery disease (CAD) in some population. However, there is a little data about NPY gene polymorphism and CAD in Iran. Therefore, we investigated the relationship between NPY gene 1128T>C and the outbreak of CAD in Iran. Methods: A total of 1061 subjected were recruited; 609 patients and 452 healthy subjects. Among 609 patients, 428 patients had more than 50% stenosis and 181 patients had less than 50% stenosis based on angiography. Angiogheraphy positive patients were divided into single vessel (n = 115), two vessels (n = 140), and three vessels (n = 173). Samples DNA was extracted in salting out method and the 1128T>C polymorphism and PCR-RFLP technique were recognized for all subjects. Results: A significant increasing in C allele and TC genotype frequency were observed in all patients compared with the control group (p < 0.05). Also, some subgroups of our subjects such as obese vs. non obese subjects and dyslipidemia vs. non dyslidpideamia had significantly higher TC genotype (p < 0.01). However, there were not significant differences among subgroups; metabolic syndrome vs. non-metabolic syndrome, hypertensive vs. nonhypertensive, diabetes vs. non-diabetes between polymorphism of NPY. The frequency of Pro7 substitution was 5.9% in our population. Conclusion: The frequency of T1128C polymorphism of NPY was 6% in Iranian population, which is higher than other Asian population. This polymorphism was associated with CAD in Iranian population. 633 AHSG GENE POLYMORPHISM AFFECTS PLASMA LEVELS OF NONHIGH-DENSITY LIPOPROTEIN CHOLESTEROL IN CAUCASIANS P. Suchanek, J.A. Hubacek, I. Kralova Lesna, V. Adamkova. Cardiovascular Research Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic Introduction: To evaluate the relationship between AHSG gene and plasma lipid levels. The alpha2 Heremans-Schmid glycoprotein (AHSG) gene is implicated in the regulation of body fat and insulin sensitivity. The genotype Met/Met (SNP rs4917) was associated with a marked increase in the lipolytic sensitivity to beta2-adrenoreceptor adipocyte on contrary to Thr carriers. We have evaluated the influence of common AHSG gene polymorphism (Thr248Met) on plasma lipid concentrations in 1% representative sample of the Czech population aged 25−65 years. Aim: The influence of Thr248Met polymorphisms in the AHSG gene on plasma cholesterol fractions was evaluated in 1152 men and 1345 women from the Czech population. Total, low-density lipoprotein cholesterol and HDL cholesterol levels were analyzed. Results: The Thr/Met variation in the AHSG gene was found to affect plasma on total and LDL cholesterol, showing significantly higher levels in Thr/Thr carriers than in Met/Met homozygotes. This association was observed in both men (TC 5.76±1.03 mmol/L in Thr/Thr carriers versus 5.48±0.90 mmol/L in Met/Met homozygotes; P < 0.001; LDL cholesterol 3.67±0.88 mmol/L in Thr/Thr carriers versus 3.40±0.77 mmol/L in Met/Met homozygotes; P < 0.01) and women (TC 5.77±1.17 mmol/L in Thr/Thr carriers versus 5.56±0.97 mmol/L in Met/Met homozygotes; P < 0.001; LDL cholesterol 3.63±1.05 mmol/L in Thr/Thr carriers versus 3.46±0.91 mmol/L in Met/Met homozygotes; P < 0.01). Conclusion: AHSG gene polymorphism plays a role in the genetic determination of total cholesterol and LDL cholesterol levels. This project was supported by grant NS 10513−3/2009 from the Internal Grant Agency of the Ministry of Health of the Czech Republic. 634 GENDER DEPENDENT ASSOCIATION BETWEEN KIF6 POLYMORPHISM AND RISK OF UNFAVORABLE OUTCOME IN PATIENTS SURVIVED ACUTE CORONARY SYNDROME O.S. Koroleva1 , M.A. Evdokimova1 , A.A. Pushkov2 , K.A. Blagodatskich2 , V.V. Nosikov2 , D.A. Zateyshchikov1 . 1 FSI Educational Scientific Medical Centre” of the General Management Department of the President of Russian Federation, 2 National Research Centre “GosNII Genetika”, Moscow, Russia Objectives: It is obvious that individual genetic features play important role in the unfavourable outcomes (UO) after acute coronary syndrome (ACS). We have studied association between polymorphism of KIF6 gene and risk of UO in patients after ACS.