- Email: [email protected]
Electrocardiographic biomarkers of metabolic cardiomyopathy and their association with long-term results of myocardial revascularization in men with coronary atherosclerosis
e220
Abstracts / Atherosclerosis 235 (2014) e192–e301
mellitus, these data were presented. Lp-PLA2 mass and activity levels were lower in low cardiovascular risk category of patients (p < 0.05). There was no any significant difference in Lp-PLA2 mass and activity levels between patients from moderate, high and very high risk categories. There was a moderate correlation between Lp-PLA2 mass and LpPLA2 activity levels (r ¼ 0.4, p < 0.00001). We did not find any correlation between Lp-PLA2 and hsCRP, Lp(a) levels. A moderate positive correlation between Lp-PLA2 mass and activity levels and TC, LDL-C was detected. There was also a moderate positive correlation between LpPLA2 activity and TG, uric acid and a moderate negative correlation between Lp-PLA2 activity and HDL-C levels. Conclusion: We found out that there was a relation between Lp-PLA2 levels and cardiovascular risk categories. Lp-PLA2 mass and activity levels were both associated with cardiovascular risk categories. 51 - Novel risk factors and biomarkers EAS-0341. ASSOCIATIONS OF CHEMERIN LEVELS AND LIPID SUBFRACTIONS IN NON-DIABETIC OBESE AND LEAN SUBJECTS I. Seresa, H. Lorincza, M. Katkóa, M. Harangia, S. Somodia, K. Gaála, P. Fülöpa, G. Paragha a
Department of Medicine, Univesity of Debrecen, Debrecen, Hungary
Objectives: Chemerin is a recently described adipokine expressed primarily in the white adipose tissue. Compared to lean subjects, circulating chemerin levels are significantly elevated in obese individuals and correlate positively with the prevalence of various cardiovascular risk factors including altered lipoprotein levels. To date, the impact of chemerin on lipoprotein subfractions and its role in atherosclerotic processes are still unclear. Methods: Fifty non-diabetic obese (NDO) patients and 38 lean controls matched in age and gender were enrolled. Chemerin level was measured by ELISA. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions were detected by non-gradient polyacrylamide gel electrophoresis (Lipoprint). Results: We detected significantly higher serum chemerin levels in NDO patients compared to healthy controls (590.1190.3 ng/ml vs. 405127.1 ng/ml, p<0.001). A significant positive correlation was found between chemerin and LDL-cholesterol levels, while chemerin showed a significant negative correlation with the level of HDL-cholesterol. Significant positive correlation was detected between chemerin and the ratio of small dense LDL, while chemerin correlated negatively with the mean LDL size. Also, a significant negative correlation was found between serum chemerin and the ratio of large HDL subfraction, while there were significant positive correlations between chemerin levels and intermediate and small HDL subfraction ratios, respectively. Conclusion: Chemerin may be involved in the regulation of lipoprotein metabolism in obese patients who do not show apparent abnormalities of glucose metabolism. Early changes in the distribution of the lipoprotein subfractions may contribute to the progression of atherosclerosis leading to increased cardiovascular risk. Acknowledgement: The work is supported by a grant from the Hungarian Scientific Research Fund (OTKA 84196) and by the TÁMOP-4.2.2.A-11/1/ KONV-2012-0031 project. The TÁMOP project is co-financed by the European Union and the European Social Fund. 51 - Novel risk factors and biomarkers EAS-0416. HETEROPLASMY LEVEL OF FIVE MITOCHONDRIAL MUTATIONS IN DIFFERENT TYPES OF LEUCOCYTES IN HUMAN BLOOD V.V. Sinyova, M.A. Sazonovab, A.I. Ryzhkovac, A.Y. Postnova, A.N. Orekhovb, I.A. Sobenina a Laboratory of Medical Genetics, Cardiology Research Complex MH RF, Moscow, Russia; b Laboratory of cellular mechanisms atherogenesis,
Institute of General Pathology and Patophysiology RAMS, Moscow, Russia; c Veterinary and Biology, Moscow state academy of veterinary medicine and biotechnology named K.I. Skryabin, Moscow, Russia Objectives: Mutations often occur in human mitochondrial genome. They can be both somatic and inherited. The aim of the present study was to find out if various types of blood cells (neutrophils, lymphocytes and monocytes) differ in heteroplasmy level of mutations in coding region of mitochondrial genome G13513A, C3256T, T3336C, G12315A and A1555G. Methods: Neutrophils, lymphocytes and monocytes were obtained with the help of extraction technique of different blood cell fractions by using double density gradient of ficoll-urografin. DNA was extracted by the standard phenol-chloroform method. PCR of mitochondrial genome mutations G13513A, C3256?, T3336C, G12315A and A1555G, associated with various human pathologies was performed. To verification the performed PCR an electrophoretic separation of amplicons was used. A quantitative assessment of mutant allele in mitochondrial genome was made by a new original method developed in our laboratory on the basis of pyrosequence technology. The statistical evaluation of the results was performed by using SPSS software package version 21.0 (SPSS Inc., USA). Results: According to the statistical data, significant differences in the heteroplasmy level of the investigated mutations between various cell types of human blood were not found. The only statistically significant difference is between neutrophils and lymphocytes in mutation A1555G. It may be caused by an insufficient sensibility of the method used for assessing the level of heteroplasmy below 5 percent. Conclusion: The obtained data about the assessment of heteroplasmy level in mitochondrial genome mutations A1555G, C3256?, T3336C, G12315A and G13513A suggest that in case of different pathologies, all whole blood cells, not only some particular types of them, can be used for investigation of single nucleotide substitutions of mitochondrial DNA. This article can be useful for hematologists and medical genetics specialists for DNA-diagnostics of mitochondrial cytopathies. This study was supported by the Russian Ministry of Education and Science. 51 - Novel risk factors and biomarkers EAS-0113. ELECTROCARDIOGRAPHIC BIOMARKERS OF METABOLIC CARDIOMYOPATHY AND THEIR ASSOCIATION WITH LONG-TERM RESULTS OF MYOCARDIAL REVASCULARIZATION IN MEN WITH CORONARY ATHEROSCLEROSIS N. Timoshenkoa, Y. Raginoa, Scherbakovac, M. Voevodad
A.
Chernjavskyib,
S.
Tcimbalb,
L.
a Laboratory of biochemistry, Federal State Budgetary Institution of Internal and Preventive Medicine Siberian, Novosibirsk, Russia; b Laboratory of Cardiology, Research State of Circulation Pathology Ministry of Public Health and Social Devel-opment Russia Novosibirsk, Novosibirsk, Russia; c Laboratory of Cardiology, Federal State Budgetary Institution of Internal and Preventive Medicine Siberian, Novosibirsk, Russia; d Laboratory of Molecular Genetics, Federal State Budgetary Institution of Internal and Preventive Medicine Siberian, Novosibirsk, Russia
Objectives: The aim of the study was to investigate the electrocardiographic (ECG) biomarkers of metabolic cardiomyopathy (MC) in men with coronary atherosclerosis (CA) and their association with 5-year long-term results of coronary artery bypass grafting (CABG). Methods: The study included 77 men aged 42-77 with CA. All patients before CABG was performed ECG at rest in 12 standard leads, followed by coding Minessota code. ECG markers MC - corrected interval QT, ST segment above >0.5mm, ST segment depression >0.5 mm non-ischemic type, T-wave changes, syndrome TV1>TV6 (amplitude of T in V1 exceeds the amplitude of T in V6), signs of left ventricular hypertrophy (LVH), arrhythmias were analyzed.
Abstracts / Atherosclerosis 235 (2014) e192–e301
Results: In men with CA before the CABG registered the following ECG markers of MK: arrhythmias in 38 patients, LVH - 55, the syndrome TV1>TV6 - 24, T-wave change - 58, segment ST elevation - 44, segment ST depression - 23, interval QT - 5. The results obtained 5-year course of CA after CABG. The group of men with complicated CA (adverse longterm prognosis) was revealed. A positive correlation between the presence of the syndrome TV1>TV6 and fatal in the long term was found. The relative risk of death in the 5-year period after CABG in patients with the syndrome TV1>TV6 was higher than in the group without the syndrome. A positive correlations between ST-segment elevation before CABG and fatal in the long term, and in general, the adverse long term were found. In patients with ST-segment elevation and in patients with the presence of the syndrome TV1>TV6 the relative risk of adverse late period as a whole (death, myocardial infarction, reoperation) was generally higher than of favorable. Conclusion: There is an association of ECG markers of MK (syndrome TV1>TV6, segment ST elevation) with 5-year long-term results of coronary revascularization in men with CA. 51 - Novel risk factors and biomarkers EAS-0838. INFLAMMATORY AND OXIDATIVE STRESS MARKERS IN PLASMA OF CRITICAL LIMB ISCHEMIA PATIENTS. E. Wysockaa, W. Walczakb, S. Michalakc, M. Nowickia, J. Tomczakb, L. Kruszynab, G. Oszkinisb a Department of Clinical Biochemistry and Laboratory Medicine, University of Medical Sciences, Poznan, Poland; b Department of and Vascular Surgery, Poznan University of Medical Sciences, Poland; c Department of Neurochemistry and Neuropathology, University of Medical Sciences, Poznan, Poland
Poznan General Poznan, Poznan
Objectives: Inflammation and oxidative stress are involved in atherosclerosis. Translating the meaning of mediators for clinical practice is still expected. The aim of the study was to assess plasma markers of oxidative stress and inflammation in peripheral artery disease (PAD) patients with critical limb ischemia. Methods: The study included 40 consecutive patients (26 males, 14 females), aged 6510 years with moderate and critical ischemia of lower limb, qualified for vascular surgery. Subjects were established stage 3 to 4 according to Fontaine classification and values of ankle-brachial pressure index. Computed tomography angiography (CTA) revealed levels of occlusion to classify the patients, including aorta and iliac arteries (group 1, n¼21: 15 males, 6 females), and femoral and/or popliteal arteries (group 2, n¼19: 11 males, 8 females). Fasting glucose, lipids and basic hematology test were measured among routine blood analysis, and glycated hemoglobin HbA1c by HPLC. Patients were assessed plasma Total Antioxidant Status (TAS) and products of lipid peroxidation as thiobarbituric acid-reacting substances (TBARS) spectrophotometrically, and serum concentrations of interleukin-6 (IL6), soluble CD14 (sCD14), Toll-like receptor-2 (TLR2) and Toll-like receptor-4 (TLR4), using ELISA methods. Results: 1.The groups did not differ with their age, body mass index, claudication distance (CD), lipids, HbA1c and hematology tests. 2.Group 1 presented higher sCD14 (p¼0,041) and TBARS (p¼0,043), and lower TLR2 (p¼0,007) and TLR4 (p¼0,042), as compared with group 2. The number of correlations were found in the study population (n¼40), i.e. the negative CD&sCD14 (R¼-0,54), CD&IL6 (R¼-0,46), CD&TBARS (R¼0,47) and TAS&IL6 (R¼-0,49), and positive: sCD14&TBARS (R¼0,42), sCD14&IL6 (R¼0,66), TBARS&IL6 (R¼0,64). 3.The different correlations concerning TLR2 and TLR4 were observed, when group1 and group2 were analyzed separately. Conclusion: Close cooperation of oxidative stress and inflammation characterizes the pathobiochemistry of PAD, however the contribution of particular factors may differ according to the level of artery occlusion.
e221
52 - GWAS, population genetics, Mendelian randomization EAS-0510. GENETIC VARIANTS ASSOCIATED WITH CORONARY ATHEROSCLEROSIS IN INDIANS USING A MICROARRAY APPROACH: A PILOT STUDY T. Ashavaida, N. Sripriyab, S. Ashleyb, P.A. Kadamb, P.K. Chawlab, S.A. Shahb, C.K. Pondec, R.M. Rajanic a Dept. of Lab Medicine, P.D.Hinduja National Hospital & MRC, Mumbai, India; b Research Laboratories, P.D.Hinduja National Hospital & MRC, Mumbai, India; c Dept. of Medicine, P.D.Hinduja National Hospital & MRC, Mumbai, India
Objectives: In absence of published GWAS data on coronary artery disease (CAD) in Indians, we have performed a microarray based large scale analysis of genes involved in cardiovascular and metabolic diseases for better understanding of genetic variants associated with CAD. Methods: A pilot study was undertaken wherein 150 angiographically proven cases and 150 age-genders matched angiographically negative controls were genotyped using Illumia's HumanCardio-Metabo BeadChip, a genotyping array consisting of SNP's associated with metabolic, cardiovascular and anthropometric traits. Illumina software GenomeStudio (V2011.1) was used for genotype calling. Standard quality control parameters and association testing were performed using PLINKv1.07. Results: Two individuals were found to be highly related to each other based on Identity by state in PLINK and the one with lower genotype call rate was excluded. Also one sample with genotype call rate <90% was excluded. A total of 96,847 SNPs present in the coding, intronic and UTR region of the genes on the microarray chip were included. However, due to HWE failure, MAF < 0.01 and SNP failure rate of >5%, the final number of SNP's available for analysis was 56,822 in 149 cases and 149 controls. Initial analysis indicates 212 SNP's to have p<0.005. Importantly, 23 were intronic variants of NOS1AP and 9 were coding variants in genes like COL4A1, MIA3, PDE1C, MYLK4 and MYH7. Association studies have already demonstrated a link between polymorphisms at the NOS1AP, MIA3, COL4A1 loci and CAD. MYLK4, PDE1C and MYH7 gene products are involved in functioning of cardiac muscle and smooth muscle cells (SMC). Conclusion: Though preliminary, the present study indicates that the genetic variants identified might aid in VSMC proliferation/migration alongwith increased collagen secretion thus highlighting an important role in the progression of atherosclerosis, however further analysis on a larger cohort would be necessary to substantiate this finding. 52 - GWAS, population genetics, Mendelian randomization EAS-0676. MENDELIAN RANDOMIZATION IN INFLAMMATORY CONDITIONS – THE EXCEPTION RATHER THAN THE RULE? S. Bezzina Wettingera, C. Doggenb, A. Spekc, A. Feliced, F.R. Rosendaale, P.H. Reitsmaf a Department of Applied Biomedical Science, University of Malta, Msida, Malta; b Health Technology and Services Research, University of Twente, Enschede, Netherlands; c Center for Experimental and Molecular Medicine, University of Amsterdam, Amsterdam, Netherlands; d Laboratory of Molecular Genetics, University of Malta, Msida, Malta; e Clinical Epidemiology, Leiden University, Leiden, Netherlands; f Einthoven Laboratory for Experimental Vascular Medicine, Leiden University, Leiden, Netherlands
Objectives: To assess causality of inflammatory RNA molecules for myocardial infarction (MI) using a Mendelian randomization approach. Methods: Samples were 524 men with a history of MI and 628 controls from the Study of Myocardial Infarction Leiden (SMILE). Macrophage migration inhibitory factor (MIF) G-173C, protein tyrosine phosphatase,
Abstracts / Atherosclerosis 235 (2014) e192–e301
mellitus, these data were presented. Lp-PLA2 mass and activity levels were lower in low cardiovascular risk category of patients (p < 0.05). There was no any significant difference in Lp-PLA2 mass and activity levels between patients from moderate, high and very high risk categories. There was a moderate correlation between Lp-PLA2 mass and LpPLA2 activity levels (r ¼ 0.4, p < 0.00001). We did not find any correlation between Lp-PLA2 and hsCRP, Lp(a) levels. A moderate positive correlation between Lp-PLA2 mass and activity levels and TC, LDL-C was detected. There was also a moderate positive correlation between LpPLA2 activity and TG, uric acid and a moderate negative correlation between Lp-PLA2 activity and HDL-C levels. Conclusion: We found out that there was a relation between Lp-PLA2 levels and cardiovascular risk categories. Lp-PLA2 mass and activity levels were both associated with cardiovascular risk categories. 51 - Novel risk factors and biomarkers EAS-0341. ASSOCIATIONS OF CHEMERIN LEVELS AND LIPID SUBFRACTIONS IN NON-DIABETIC OBESE AND LEAN SUBJECTS I. Seresa, H. Lorincza, M. Katkóa, M. Harangia, S. Somodia, K. Gaála, P. Fülöpa, G. Paragha a
Department of Medicine, Univesity of Debrecen, Debrecen, Hungary
Objectives: Chemerin is a recently described adipokine expressed primarily in the white adipose tissue. Compared to lean subjects, circulating chemerin levels are significantly elevated in obese individuals and correlate positively with the prevalence of various cardiovascular risk factors including altered lipoprotein levels. To date, the impact of chemerin on lipoprotein subfractions and its role in atherosclerotic processes are still unclear. Methods: Fifty non-diabetic obese (NDO) patients and 38 lean controls matched in age and gender were enrolled. Chemerin level was measured by ELISA. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions were detected by non-gradient polyacrylamide gel electrophoresis (Lipoprint). Results: We detected significantly higher serum chemerin levels in NDO patients compared to healthy controls (590.1190.3 ng/ml vs. 405127.1 ng/ml, p<0.001). A significant positive correlation was found between chemerin and LDL-cholesterol levels, while chemerin showed a significant negative correlation with the level of HDL-cholesterol. Significant positive correlation was detected between chemerin and the ratio of small dense LDL, while chemerin correlated negatively with the mean LDL size. Also, a significant negative correlation was found between serum chemerin and the ratio of large HDL subfraction, while there were significant positive correlations between chemerin levels and intermediate and small HDL subfraction ratios, respectively. Conclusion: Chemerin may be involved in the regulation of lipoprotein metabolism in obese patients who do not show apparent abnormalities of glucose metabolism. Early changes in the distribution of the lipoprotein subfractions may contribute to the progression of atherosclerosis leading to increased cardiovascular risk. Acknowledgement: The work is supported by a grant from the Hungarian Scientific Research Fund (OTKA 84196) and by the TÁMOP-4.2.2.A-11/1/ KONV-2012-0031 project. The TÁMOP project is co-financed by the European Union and the European Social Fund. 51 - Novel risk factors and biomarkers EAS-0416. HETEROPLASMY LEVEL OF FIVE MITOCHONDRIAL MUTATIONS IN DIFFERENT TYPES OF LEUCOCYTES IN HUMAN BLOOD V.V. Sinyova, M.A. Sazonovab, A.I. Ryzhkovac, A.Y. Postnova, A.N. Orekhovb, I.A. Sobenina a Laboratory of Medical Genetics, Cardiology Research Complex MH RF, Moscow, Russia; b Laboratory of cellular mechanisms atherogenesis,
Institute of General Pathology and Patophysiology RAMS, Moscow, Russia; c Veterinary and Biology, Moscow state academy of veterinary medicine and biotechnology named K.I. Skryabin, Moscow, Russia Objectives: Mutations often occur in human mitochondrial genome. They can be both somatic and inherited. The aim of the present study was to find out if various types of blood cells (neutrophils, lymphocytes and monocytes) differ in heteroplasmy level of mutations in coding region of mitochondrial genome G13513A, C3256T, T3336C, G12315A and A1555G. Methods: Neutrophils, lymphocytes and monocytes were obtained with the help of extraction technique of different blood cell fractions by using double density gradient of ficoll-urografin. DNA was extracted by the standard phenol-chloroform method. PCR of mitochondrial genome mutations G13513A, C3256?, T3336C, G12315A and A1555G, associated with various human pathologies was performed. To verification the performed PCR an electrophoretic separation of amplicons was used. A quantitative assessment of mutant allele in mitochondrial genome was made by a new original method developed in our laboratory on the basis of pyrosequence technology. The statistical evaluation of the results was performed by using SPSS software package version 21.0 (SPSS Inc., USA). Results: According to the statistical data, significant differences in the heteroplasmy level of the investigated mutations between various cell types of human blood were not found. The only statistically significant difference is between neutrophils and lymphocytes in mutation A1555G. It may be caused by an insufficient sensibility of the method used for assessing the level of heteroplasmy below 5 percent. Conclusion: The obtained data about the assessment of heteroplasmy level in mitochondrial genome mutations A1555G, C3256?, T3336C, G12315A and G13513A suggest that in case of different pathologies, all whole blood cells, not only some particular types of them, can be used for investigation of single nucleotide substitutions of mitochondrial DNA. This article can be useful for hematologists and medical genetics specialists for DNA-diagnostics of mitochondrial cytopathies. This study was supported by the Russian Ministry of Education and Science. 51 - Novel risk factors and biomarkers EAS-0113. ELECTROCARDIOGRAPHIC BIOMARKERS OF METABOLIC CARDIOMYOPATHY AND THEIR ASSOCIATION WITH LONG-TERM RESULTS OF MYOCARDIAL REVASCULARIZATION IN MEN WITH CORONARY ATHEROSCLEROSIS N. Timoshenkoa, Y. Raginoa, Scherbakovac, M. Voevodad
A.
Chernjavskyib,
S.
Tcimbalb,
L.
a Laboratory of biochemistry, Federal State Budgetary Institution of Internal and Preventive Medicine Siberian, Novosibirsk, Russia; b Laboratory of Cardiology, Research State of Circulation Pathology Ministry of Public Health and Social Devel-opment Russia Novosibirsk, Novosibirsk, Russia; c Laboratory of Cardiology, Federal State Budgetary Institution of Internal and Preventive Medicine Siberian, Novosibirsk, Russia; d Laboratory of Molecular Genetics, Federal State Budgetary Institution of Internal and Preventive Medicine Siberian, Novosibirsk, Russia
Objectives: The aim of the study was to investigate the electrocardiographic (ECG) biomarkers of metabolic cardiomyopathy (MC) in men with coronary atherosclerosis (CA) and their association with 5-year long-term results of coronary artery bypass grafting (CABG). Methods: The study included 77 men aged 42-77 with CA. All patients before CABG was performed ECG at rest in 12 standard leads, followed by coding Minessota code. ECG markers MC - corrected interval QT, ST segment above >0.5mm, ST segment depression >0.5 mm non-ischemic type, T-wave changes, syndrome TV1>TV6 (amplitude of T in V1 exceeds the amplitude of T in V6), signs of left ventricular hypertrophy (LVH), arrhythmias were analyzed.
Abstracts / Atherosclerosis 235 (2014) e192–e301
Results: In men with CA before the CABG registered the following ECG markers of MK: arrhythmias in 38 patients, LVH - 55, the syndrome TV1>TV6 - 24, T-wave change - 58, segment ST elevation - 44, segment ST depression - 23, interval QT - 5. The results obtained 5-year course of CA after CABG. The group of men with complicated CA (adverse longterm prognosis) was revealed. A positive correlation between the presence of the syndrome TV1>TV6 and fatal in the long term was found. The relative risk of death in the 5-year period after CABG in patients with the syndrome TV1>TV6 was higher than in the group without the syndrome. A positive correlations between ST-segment elevation before CABG and fatal in the long term, and in general, the adverse long term were found. In patients with ST-segment elevation and in patients with the presence of the syndrome TV1>TV6 the relative risk of adverse late period as a whole (death, myocardial infarction, reoperation) was generally higher than of favorable. Conclusion: There is an association of ECG markers of MK (syndrome TV1>TV6, segment ST elevation) with 5-year long-term results of coronary revascularization in men with CA. 51 - Novel risk factors and biomarkers EAS-0838. INFLAMMATORY AND OXIDATIVE STRESS MARKERS IN PLASMA OF CRITICAL LIMB ISCHEMIA PATIENTS. E. Wysockaa, W. Walczakb, S. Michalakc, M. Nowickia, J. Tomczakb, L. Kruszynab, G. Oszkinisb a Department of Clinical Biochemistry and Laboratory Medicine, University of Medical Sciences, Poznan, Poland; b Department of and Vascular Surgery, Poznan University of Medical Sciences, Poland; c Department of Neurochemistry and Neuropathology, University of Medical Sciences, Poznan, Poland
Poznan General Poznan, Poznan
Objectives: Inflammation and oxidative stress are involved in atherosclerosis. Translating the meaning of mediators for clinical practice is still expected. The aim of the study was to assess plasma markers of oxidative stress and inflammation in peripheral artery disease (PAD) patients with critical limb ischemia. Methods: The study included 40 consecutive patients (26 males, 14 females), aged 6510 years with moderate and critical ischemia of lower limb, qualified for vascular surgery. Subjects were established stage 3 to 4 according to Fontaine classification and values of ankle-brachial pressure index. Computed tomography angiography (CTA) revealed levels of occlusion to classify the patients, including aorta and iliac arteries (group 1, n¼21: 15 males, 6 females), and femoral and/or popliteal arteries (group 2, n¼19: 11 males, 8 females). Fasting glucose, lipids and basic hematology test were measured among routine blood analysis, and glycated hemoglobin HbA1c by HPLC. Patients were assessed plasma Total Antioxidant Status (TAS) and products of lipid peroxidation as thiobarbituric acid-reacting substances (TBARS) spectrophotometrically, and serum concentrations of interleukin-6 (IL6), soluble CD14 (sCD14), Toll-like receptor-2 (TLR2) and Toll-like receptor-4 (TLR4), using ELISA methods. Results: 1.The groups did not differ with their age, body mass index, claudication distance (CD), lipids, HbA1c and hematology tests. 2.Group 1 presented higher sCD14 (p¼0,041) and TBARS (p¼0,043), and lower TLR2 (p¼0,007) and TLR4 (p¼0,042), as compared with group 2. The number of correlations were found in the study population (n¼40), i.e. the negative CD&sCD14 (R¼-0,54), CD&IL6 (R¼-0,46), CD&TBARS (R¼0,47) and TAS&IL6 (R¼-0,49), and positive: sCD14&TBARS (R¼0,42), sCD14&IL6 (R¼0,66), TBARS&IL6 (R¼0,64). 3.The different correlations concerning TLR2 and TLR4 were observed, when group1 and group2 were analyzed separately. Conclusion: Close cooperation of oxidative stress and inflammation characterizes the pathobiochemistry of PAD, however the contribution of particular factors may differ according to the level of artery occlusion.
e221
52 - GWAS, population genetics, Mendelian randomization EAS-0510. GENETIC VARIANTS ASSOCIATED WITH CORONARY ATHEROSCLEROSIS IN INDIANS USING A MICROARRAY APPROACH: A PILOT STUDY T. Ashavaida, N. Sripriyab, S. Ashleyb, P.A. Kadamb, P.K. Chawlab, S.A. Shahb, C.K. Pondec, R.M. Rajanic a Dept. of Lab Medicine, P.D.Hinduja National Hospital & MRC, Mumbai, India; b Research Laboratories, P.D.Hinduja National Hospital & MRC, Mumbai, India; c Dept. of Medicine, P.D.Hinduja National Hospital & MRC, Mumbai, India
Objectives: In absence of published GWAS data on coronary artery disease (CAD) in Indians, we have performed a microarray based large scale analysis of genes involved in cardiovascular and metabolic diseases for better understanding of genetic variants associated with CAD. Methods: A pilot study was undertaken wherein 150 angiographically proven cases and 150 age-genders matched angiographically negative controls were genotyped using Illumia's HumanCardio-Metabo BeadChip, a genotyping array consisting of SNP's associated with metabolic, cardiovascular and anthropometric traits. Illumina software GenomeStudio (V2011.1) was used for genotype calling. Standard quality control parameters and association testing were performed using PLINKv1.07. Results: Two individuals were found to be highly related to each other based on Identity by state in PLINK and the one with lower genotype call rate was excluded. Also one sample with genotype call rate <90% was excluded. A total of 96,847 SNPs present in the coding, intronic and UTR region of the genes on the microarray chip were included. However, due to HWE failure, MAF < 0.01 and SNP failure rate of >5%, the final number of SNP's available for analysis was 56,822 in 149 cases and 149 controls. Initial analysis indicates 212 SNP's to have p<0.005. Importantly, 23 were intronic variants of NOS1AP and 9 were coding variants in genes like COL4A1, MIA3, PDE1C, MYLK4 and MYH7. Association studies have already demonstrated a link between polymorphisms at the NOS1AP, MIA3, COL4A1 loci and CAD. MYLK4, PDE1C and MYH7 gene products are involved in functioning of cardiac muscle and smooth muscle cells (SMC). Conclusion: Though preliminary, the present study indicates that the genetic variants identified might aid in VSMC proliferation/migration alongwith increased collagen secretion thus highlighting an important role in the progression of atherosclerosis, however further analysis on a larger cohort would be necessary to substantiate this finding. 52 - GWAS, population genetics, Mendelian randomization EAS-0676. MENDELIAN RANDOMIZATION IN INFLAMMATORY CONDITIONS – THE EXCEPTION RATHER THAN THE RULE? S. Bezzina Wettingera, C. Doggenb, A. Spekc, A. Feliced, F.R. Rosendaale, P.H. Reitsmaf a Department of Applied Biomedical Science, University of Malta, Msida, Malta; b Health Technology and Services Research, University of Twente, Enschede, Netherlands; c Center for Experimental and Molecular Medicine, University of Amsterdam, Amsterdam, Netherlands; d Laboratory of Molecular Genetics, University of Malta, Msida, Malta; e Clinical Epidemiology, Leiden University, Leiden, Netherlands; f Einthoven Laboratory for Experimental Vascular Medicine, Leiden University, Leiden, Netherlands
Objectives: To assess causality of inflammatory RNA molecules for myocardial infarction (MI) using a Mendelian randomization approach. Methods: Samples were 524 men with a history of MI and 628 controls from the Study of Myocardial Infarction Leiden (SMILE). Macrophage migration inhibitory factor (MIF) G-173C, protein tyrosine phosphatase,