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ASSOCIATION OF GLYCOPROTEIN MEMBRANE RECEPTOR POLYMORPHISMS WITH CORONARY ARTERY DISEASE IN INDIAN POPULATION
Poster Sessions PO24 Genetic polymorphisms and cardiovascular risk Conclusions: The HL-514C/T and CETP I405V were very similar with relation to lipids and lipoproteins’ variations and confered an anti-atherogenic plasma profile in Hyper-A. PO24-366
EFFECTS OF APOLIPOPROTEIN(A) SIZE POLYMORPHISM AND LIPOPROTEIN(A) CONCETRATIONS COMBINED WITH OTHER RISK FACTORS ON CAD DEVELOPMENT
Z. Jelic-Ivanovic 1 , N. Bogavac-Stanojevic 1 , V. Spasojevic-Kalimanovska 1 , S. Spasic 1 , L. Memon 2 , D. Kalimanovska-Ostric 3 . 1 Institute of Medical Biochemistry, Faculty of Pharmacy, Belgrade, Serbia; 2 Clinical Centre; 3 Institute for Cardiovascular Diseases, Clinical Centre of Serbia, Belgrade, Serbia
PO24-367
ASSOCIATION OF GLYCOPROTEIN MEMBRANE RECEPTOR POLYMORPHISMS WITH CORONARY ARTERY DISEASE IN INDIAN POPULATION
T.F. Ashavaid 1 , J.S. Morey 2 . 1 Research Laboratories and Dept., of Laboratory Medicine, P.D. Hinduja National Hospital & Medical Research Center, V.S. Marg, Mahim, Mumbai-16, Maharashtra, INDIA; 2 Research Laboratories, P.D. Hinduja National Hospital & Medical Research Center, V.S. Marg, Mahim, Mumbai-16, Maharashtra, INDIA Background and Aims: Thrombus formation is influenced by environmental and genetic factors and occurs when the normal homeostasis is disturbed. It is initiated by adhesion of platelets to subendothelial structures and is influenced by polymorphisms of the various platelet membrane glycoproteins viz. GPIIb/IIIa (PLA1/A2), GPIb/IX/IV (HPA2a/2b, VNTR), and GPIa/IIa (C807T). Methods: We studied the association of the polymorphisms with CAD in 100 CAD patients and 100 healthy controls. All patients underwent stent implant at our hospital and were on antiplatelet therapy (Clopidogrel and Aspirin) postoperatively. Blood samples collected in EDTA tubes were used for DNA extraction and subsequently genotyped. Results: The frequency of PLA1/A2 polymorphism in the patients was lesser than in our controls (14% vs 20%) suggesting the lack of association with CAD in our population. Similarly the other three polymorphisms also did not show any association with CAD. As the PLA1/A2 polymorphism has also been associated with risk of restenosis in stent implanted cases, we further did a follow up of the patients for a period of 6 weeks. But the polymorphism failed to show any significant association. Conclusion: It may be concluded that the platelet receptor polymorphisms may not be associated with risk of CAD in our population, though further study on a larger number of cohorts will support the findings.
LACK OF ASSOCIATION BETWEEN MCP-1 GENE POLYMORPHISM (–2518G/A) AND PREMATURE CORONARY ARTERY DISEASE
F.S. Cam 1 , C. Sekuri 2 , A. Sagcan 2 , E. Ercan 2 , I. Tengiz 2 , E. Alioglu 2 , A. Berdeli 3 . 1 Department of Medical Biology and Genetics, Celal Bayar University, Faculty of Medicine, Manisa, Turkey; 2 Dept of Cardiology, Kent Hospital, Izmir, Turkey; 3 Department of Pediatrics, Molecular Diagnostics Laboratory, Ege University, Faculty of Medicine, Izmir, Turkey Background and aims: Monocyte chemoattractant protein-1 (MCP-1) has been suggested to play an important role in the initiation of atherosclerosis and postulated to have a crucial role in monocyte recruitment into the subendothelial lesions. Recent studies have demonstrated that MCP-1 -2518 G/A polymorphism was associated with susceptibility to coronary arterial disease. We investigated the role of this polymorphism in patients with premature coronary artery disease (CAD). Methods: Genomic DNA was collected from 171 premature CAD patients and 151 healthy individuals. The MCP-1 -2518 G/A polymorphism was genotyped using PCR-Restriction Enzyme digestion. Results: Genotype and allele frequencies were not different in premature CAD and control groups (AA: 49.7%; AG: 40.3%; GG: 10.0% in premature CAD groups, AA: 53.7%; AG: 34.4%; GG: 11.9% in controls, p= 0.53). The prevalence of the G allele was 0.302 in patients and 0.291 in controls. Conclusions: Our data demonstrate that the MCP-1 –2518G/A polymorphism is not associated with premature CAD. Further studies are needed to elucidate the role of this polymorphism in the pathogenesis of CAD in various populations. PO24-369
THE ASSOCIATION OF ARTERIAL FUNCTION AND FUNCTIONAL POLYMORPHISMS OF RAAS IN KOREANS
J. Suh 1,2 , S. Choi 1,2 , J. Park 1 , H. Kang 1 , B. Koo 1 , Y. Kim 1 , S. Oh 1 , H. Kim 1 , D. Sohn 1 , B. Oh 1 . 1 Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital; 2 Healthcare system Gangnam Center, Seoul National University Hospital Background: Subclinical arterial dysfunction is suggested as a surrogate marker of atherosclerotic cardiovascular disease. Renin-AngiotensinAldosterone system (RAAS) plays an important role in the regulation of vascular tone and its functional polymorphisms are associated with cardiovascular events. However, it is not well known whether they are related with subclincial arterial dysfunction. We evaluated the correlation between arterial function and various functional polymorphisms of RAAS in Koreans. Methods: From Mar 2004 to Mar 2007, people (n=534, 58.5±9.2 yrs) who visited our center for routine check and agreed to gene analysis were prospectively enrolled. Sixty eight percent of them were male, 51% had hypertension and 12% had diabetes mellitus. Flow-mediated dilatation (FMD), aortic pulse wave velocity (PWV), ankle-brachial index (ABI) and intima-media thickness (IMT) were measured as markers of arterial function. Also, we analyzed angiotensinogen (AGT M235T), ACE (278-bp I/D) and angiotensin type 1 receptor (ATR1, A1166C) polymorphisms. Results: Frequency of T allele in AGT was 81.9% and A allele in ATR1 was 6.5%. Frequency of 278-bp deletion was 40.0% in ACE polymorphism. Eighty seven people (16.3%) showed MT/TT (AGT) and DD genotype (ACE). They showed less FMD (11.9±3.1% vs. 13.0±4.1%, p=0.007) and more IMT (0.82±0.23mm vs. 0.79±0.23mm, p=0.034) compared to other genotypes. Other markers of arterial function were not different between two groups. Conclusion: People who have specific combination of RAAS polymorphisms such as MT/TT+DD genotype showed earlier sign of endothelial dysfunction (FMD) and subclinical atherosclerosis (IMT). This difference may be led to more frequent cardiovascular events in people with this genotype. PO24-370
UPDATE AND ANALYSIS OF THE UCL LOW DENSITY LIPOPROTEIN RECEPTOR GENE (LDLR) FAMILIAL HYPERCHOLESTEROLEMIA (FH) DATABASE
S.E. Leigh, R.A. Whittall, C.S. Hubbart, S.E. Humphries. Cardiovascular Genetics Centre, Royal Free & UCL Medical School, London, UK Aims: To review and update existing entries in the UCL LDLR FH database 77th Congress of the European Atherosclerosis Society, April 26–29, 2008, Istanbul, Turkey
POSTER SESSIONS
Background and aims: High serum lipoprotein(a) concentrations and small apolipoprotein(a) isoforms are known to be associated with coronary artery disease (CAD). We investigated their effects on CAD development in the presence/absence of other risk factors. Methods: 279 patients with CAD assessed by coronary angiography and 280 healthy individuals were included in the study. BMI, waistto-hip ratio (WHR), smoking status and the presence of hypertension were recorded. Apolipoprotein(a) phenotyping was performed by submarine SDS-electrophoresis and immunoblotting. Serum lipids, lipoproteins, apolipoproteins and hs-CRP were measured by standard laboratory methods. Results: High lipoprotein(a) concentrations significantly increased the risk for CAD if combined with the presence of hypertension (OR = 2.046), BMI ≥ 29,4 (OR = 3.412), kg/m2 , WHR ≥ 0,97 (OR = 6.349), high total cholesterol (OR = 2.386), LDL-C (OR = 2.720), hs-CRP (OR = 2.204), apolipoprotein B (OR = 3.852), or low HDL-C (OR = 2.136) or apolipoprotein A-I (OR = 3.427). Small apolipoprotein(a) isoforms (with < 24 kringle 4 type 2 repeats) significantly increased the risk in non-smokers (OR = 2.819), individuals with BMI ≤ 24,1, kg/m2 (OR = 3.317), hypertension (OR = 3.123), high total cholesterol (OR = 3.528), triglycerides (OR = 4.297), LDL-C (OR = 4.395), hs-CRP (OR = 2.204), apolipoprotein B (OR = 3.852), or low HDL-C (OR = 2.646), or apolipoprotein A-I (OR = 3.427). Conclusions: Our results have shown that high lipoprotein(a) concentrations and small apolipoprotein(a) isoforms generally tend to increase the risk for CAD development when combined with other risk factors.
PO24-368
107
EFFECTS OF APOLIPOPROTEIN(A) SIZE POLYMORPHISM AND LIPOPROTEIN(A) CONCETRATIONS COMBINED WITH OTHER RISK FACTORS ON CAD DEVELOPMENT
Z. Jelic-Ivanovic 1 , N. Bogavac-Stanojevic 1 , V. Spasojevic-Kalimanovska 1 , S. Spasic 1 , L. Memon 2 , D. Kalimanovska-Ostric 3 . 1 Institute of Medical Biochemistry, Faculty of Pharmacy, Belgrade, Serbia; 2 Clinical Centre; 3 Institute for Cardiovascular Diseases, Clinical Centre of Serbia, Belgrade, Serbia
PO24-367
ASSOCIATION OF GLYCOPROTEIN MEMBRANE RECEPTOR POLYMORPHISMS WITH CORONARY ARTERY DISEASE IN INDIAN POPULATION
T.F. Ashavaid 1 , J.S. Morey 2 . 1 Research Laboratories and Dept., of Laboratory Medicine, P.D. Hinduja National Hospital & Medical Research Center, V.S. Marg, Mahim, Mumbai-16, Maharashtra, INDIA; 2 Research Laboratories, P.D. Hinduja National Hospital & Medical Research Center, V.S. Marg, Mahim, Mumbai-16, Maharashtra, INDIA Background and Aims: Thrombus formation is influenced by environmental and genetic factors and occurs when the normal homeostasis is disturbed. It is initiated by adhesion of platelets to subendothelial structures and is influenced by polymorphisms of the various platelet membrane glycoproteins viz. GPIIb/IIIa (PLA1/A2), GPIb/IX/IV (HPA2a/2b, VNTR), and GPIa/IIa (C807T). Methods: We studied the association of the polymorphisms with CAD in 100 CAD patients and 100 healthy controls. All patients underwent stent implant at our hospital and were on antiplatelet therapy (Clopidogrel and Aspirin) postoperatively. Blood samples collected in EDTA tubes were used for DNA extraction and subsequently genotyped. Results: The frequency of PLA1/A2 polymorphism in the patients was lesser than in our controls (14% vs 20%) suggesting the lack of association with CAD in our population. Similarly the other three polymorphisms also did not show any association with CAD. As the PLA1/A2 polymorphism has also been associated with risk of restenosis in stent implanted cases, we further did a follow up of the patients for a period of 6 weeks. But the polymorphism failed to show any significant association. Conclusion: It may be concluded that the platelet receptor polymorphisms may not be associated with risk of CAD in our population, though further study on a larger number of cohorts will support the findings.
LACK OF ASSOCIATION BETWEEN MCP-1 GENE POLYMORPHISM (–2518G/A) AND PREMATURE CORONARY ARTERY DISEASE
F.S. Cam 1 , C. Sekuri 2 , A. Sagcan 2 , E. Ercan 2 , I. Tengiz 2 , E. Alioglu 2 , A. Berdeli 3 . 1 Department of Medical Biology and Genetics, Celal Bayar University, Faculty of Medicine, Manisa, Turkey; 2 Dept of Cardiology, Kent Hospital, Izmir, Turkey; 3 Department of Pediatrics, Molecular Diagnostics Laboratory, Ege University, Faculty of Medicine, Izmir, Turkey Background and aims: Monocyte chemoattractant protein-1 (MCP-1) has been suggested to play an important role in the initiation of atherosclerosis and postulated to have a crucial role in monocyte recruitment into the subendothelial lesions. Recent studies have demonstrated that MCP-1 -2518 G/A polymorphism was associated with susceptibility to coronary arterial disease. We investigated the role of this polymorphism in patients with premature coronary artery disease (CAD). Methods: Genomic DNA was collected from 171 premature CAD patients and 151 healthy individuals. The MCP-1 -2518 G/A polymorphism was genotyped using PCR-Restriction Enzyme digestion. Results: Genotype and allele frequencies were not different in premature CAD and control groups (AA: 49.7%; AG: 40.3%; GG: 10.0% in premature CAD groups, AA: 53.7%; AG: 34.4%; GG: 11.9% in controls, p= 0.53). The prevalence of the G allele was 0.302 in patients and 0.291 in controls. Conclusions: Our data demonstrate that the MCP-1 –2518G/A polymorphism is not associated with premature CAD. Further studies are needed to elucidate the role of this polymorphism in the pathogenesis of CAD in various populations. PO24-369
THE ASSOCIATION OF ARTERIAL FUNCTION AND FUNCTIONAL POLYMORPHISMS OF RAAS IN KOREANS
J. Suh 1,2 , S. Choi 1,2 , J. Park 1 , H. Kang 1 , B. Koo 1 , Y. Kim 1 , S. Oh 1 , H. Kim 1 , D. Sohn 1 , B. Oh 1 . 1 Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital; 2 Healthcare system Gangnam Center, Seoul National University Hospital Background: Subclinical arterial dysfunction is suggested as a surrogate marker of atherosclerotic cardiovascular disease. Renin-AngiotensinAldosterone system (RAAS) plays an important role in the regulation of vascular tone and its functional polymorphisms are associated with cardiovascular events. However, it is not well known whether they are related with subclincial arterial dysfunction. We evaluated the correlation between arterial function and various functional polymorphisms of RAAS in Koreans. Methods: From Mar 2004 to Mar 2007, people (n=534, 58.5±9.2 yrs) who visited our center for routine check and agreed to gene analysis were prospectively enrolled. Sixty eight percent of them were male, 51% had hypertension and 12% had diabetes mellitus. Flow-mediated dilatation (FMD), aortic pulse wave velocity (PWV), ankle-brachial index (ABI) and intima-media thickness (IMT) were measured as markers of arterial function. Also, we analyzed angiotensinogen (AGT M235T), ACE (278-bp I/D) and angiotensin type 1 receptor (ATR1, A1166C) polymorphisms. Results: Frequency of T allele in AGT was 81.9% and A allele in ATR1 was 6.5%. Frequency of 278-bp deletion was 40.0% in ACE polymorphism. Eighty seven people (16.3%) showed MT/TT (AGT) and DD genotype (ACE). They showed less FMD (11.9±3.1% vs. 13.0±4.1%, p=0.007) and more IMT (0.82±0.23mm vs. 0.79±0.23mm, p=0.034) compared to other genotypes. Other markers of arterial function were not different between two groups. Conclusion: People who have specific combination of RAAS polymorphisms such as MT/TT+DD genotype showed earlier sign of endothelial dysfunction (FMD) and subclinical atherosclerosis (IMT). This difference may be led to more frequent cardiovascular events in people with this genotype. PO24-370
UPDATE AND ANALYSIS OF THE UCL LOW DENSITY LIPOPROTEIN RECEPTOR GENE (LDLR) FAMILIAL HYPERCHOLESTEROLEMIA (FH) DATABASE
S.E. Leigh, R.A. Whittall, C.S. Hubbart, S.E. Humphries. Cardiovascular Genetics Centre, Royal Free & UCL Medical School, London, UK Aims: To review and update existing entries in the UCL LDLR FH database 77th Congress of the European Atherosclerosis Society, April 26–29, 2008, Istanbul, Turkey
POSTER SESSIONS
Background and aims: High serum lipoprotein(a) concentrations and small apolipoprotein(a) isoforms are known to be associated with coronary artery disease (CAD). We investigated their effects on CAD development in the presence/absence of other risk factors. Methods: 279 patients with CAD assessed by coronary angiography and 280 healthy individuals were included in the study. BMI, waistto-hip ratio (WHR), smoking status and the presence of hypertension were recorded. Apolipoprotein(a) phenotyping was performed by submarine SDS-electrophoresis and immunoblotting. Serum lipids, lipoproteins, apolipoproteins and hs-CRP were measured by standard laboratory methods. Results: High lipoprotein(a) concentrations significantly increased the risk for CAD if combined with the presence of hypertension (OR = 2.046), BMI ≥ 29,4 (OR = 3.412), kg/m2 , WHR ≥ 0,97 (OR = 6.349), high total cholesterol (OR = 2.386), LDL-C (OR = 2.720), hs-CRP (OR = 2.204), apolipoprotein B (OR = 3.852), or low HDL-C (OR = 2.136) or apolipoprotein A-I (OR = 3.427). Small apolipoprotein(a) isoforms (with < 24 kringle 4 type 2 repeats) significantly increased the risk in non-smokers (OR = 2.819), individuals with BMI ≤ 24,1, kg/m2 (OR = 3.317), hypertension (OR = 3.123), high total cholesterol (OR = 3.528), triglycerides (OR = 4.297), LDL-C (OR = 4.395), hs-CRP (OR = 2.204), apolipoprotein B (OR = 3.852), or low HDL-C (OR = 2.646), or apolipoprotein A-I (OR = 3.427). Conclusions: Our results have shown that high lipoprotein(a) concentrations and small apolipoprotein(a) isoforms generally tend to increase the risk for CAD development when combined with other risk factors.
PO24-368
107