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ASSOCIATION OF PLASMA ANGIOTENSIN- CONVERTING ENZYME ACTIVITY AND GENE POLYMORPHISM IN TUNISIAN PATIENTS AFFECTED WITH MYOCARDIAL INFARCTION
106 PO24-362
Poster Sessions PO24 Genetic polymorphisms and cardiovascular risk ASSOCIATION OF PLASMA ANGIOTENSINCONVERTING ENZYME ACTIVITY AND GENE POLYMORPHISM IN TUNISIAN PATIENTS AFFECTED WITH MYOCARDIAL INFARCTION
S. Mehri 1,5 , B. Baudin 2 , C. Mahjoub 1 , F. Guemira 3 , M. Rachid 4 , B. Bénéteau-Burnat 2 , S. Ben Arab 1 , M. Hammami 5 . 1 Unité d‘Epidemiologie Génétique et Moleculaire à la Faculté de Médecine de Tunis. Tunisie; 2 Biochimie A, Hopital Saint-Antoine, 184 rue du faubourg Saint-Antoine, 75571 Paris cedex 12, France; 3 Laboratoire de Biochimie et Biologie Moleculaire à l’Hopital Salah Azaiez de Tunis; 4 Services des explorations fonctionnelles Cardiologiques. Hopital La Rabta Tunis. Tunisie; 5 Biochimistry Laboratory UR Background and aims: The Angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism has been studied as a risk factor for acute myocardial infarction (MI) in different populations with conflicting results. Individuals homozygous for the deletion have a higher level of circulating enzyme. The present study is the first report in Tunisia to investigate the association between the ACE gene I/D polymorphism and MI and to examine the relationship between this polymorphism and the serum ACE activity. Material/Methods: ACE I/D polymorphism genotypes were determined by PCR in 101 patients affected with MI and 206 control subjects without history of coronary disease, originated from the same areas. ACE activity was determined by SYNCHRON CX-4 analyser with furylacrylolphenylalanyl- glycyl-glycine as specific substrates. Results: Allele D frequency was 83.2% in patients affected with MI versus 50.7% in control subjects. There was a significant association between D allele and MI (OR =3.55; 95% CI; 2.65-5.33; p <0.001). The mean serum ACE activities was higher in homozygous DD than in I carriers (94.11±47.96 vs 74.31±33.25 and 58.26±13.59 U/L respectively). The serum ACE activities were significantly different between D and I carries in male patients affected with MI. The mean serum ACE activity of D and I was 91.70±46.52 and 67.33±27.14 U/L respectively. Significant ACE activity was found with allele D (p < 0.001). Conclusions: D allele has been associated with increased serum ACE activity. These findings may implicate I/D ACE polymorphism as a genetic marker of MI risk in Tunisian population. PO24-363
EFFECT OF THE RESISTIN -420C>G POLYMORPHISM ON CARDIOVASCULAR DISEASE, DIABETES AND MORTALITY
M.M. Hoffmann 1 , I. Futter 1 , S. Pilz 2 , G. Weihrauch 2 , U. Seelhorst 3 , B.R. Winkelmann 4 , B.O. Boehm 5 , W. Maerz 6 . 1 Clinical Chemistry, University Medical Center, Freiburg, Germany; 2 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, Austria; 3 LURIC Study nonprofit LLC, Freiburg, Germany; 4 Cardiology Group, Frankfurt Sachsenhausen, Germany; 5 Division of Endocrinology and Diabetes, University of Ulm, Germany; 6 Synlab Center of Laboratory Diagnostics, Heidelberg, Germany Resistin is an adipokine involved in the regulation of glucose homeostasis in rodents and probably in humans, too. Apart from this function there is growing evidence of a proatherosclerotic effect of resistin in vascular diseases. A common polymorphism (-420C>G) in the promoter of the resistin gene (RETN) has been described to be associated with resistin plasma levels and susceptibility to type II diabetes. The aim of this study was to investigate the association of this polymorphism with angiographic coronary artery disease, myocardial infarction, type II diabetes, and mortality. Design and results: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study is a prospective study of white subjects who had undergone coronary angiography, including 2553 patients with angiographically documented CAD and 698 individuals in whom CAD had been ruled out by angiography. We could not find any association between a specific promoter genotype of RETN and resistin plasma levels, the risk for CAD, the coronary status, MI or type II diabetes, even after adjustment for traditional risk factors like smoking, gender, and hypertension. Among the 3251 LURIC study participants included in this examination, 622 deaths (19.1%) occurred during a median observation time of 5.4 years. Regardless of whether or not we adjusted for age, sex, and conventional risk factors, the RETN polymorphism showed no association with mortality from all causes or with cardiovascular mortality. Conclusion: An association between the RETN -420C>G polymor-
phism and CAD, MI or type II diabetes at least in Caucasians is unlikely. PO24-364
EVALUATION OF PARAOXONASE-1 GENE POLYMORPHISM AND SERUM PARAOXONASE ACTIVITY AS A CARDIOVASCULAR RISK
T. Bayrak 1 , A. Deniz 2 , L. Tokgozoglu 2 , B. Yavuz 2 , E. Demirpence 1 , A. Bayrak 1 , K. Kilinc 3 , B. Salancı 4 , M. Alikasifoglu 3 , E. Tuncbilek 3 . 1 Hacettepe University Faculty of Medicine Department of Biochemistry; 2 Hacettepe University Faculty of Medicine Department of Cadiology; 3 Hacettepe University Faculty of Medicine Department of Pediatrics, Division of Genetics; 4 Hacettepe University Faculty of Medicine Department of Nucleer Medicine Background: Paraoxonase-1 (PON1) is a high density lipoprotein (HDL)associated enzyme. It has been shown that PON1 protects low density lipoprotein (LDL) particles from oxidative injury by hydrolysing lipoperoxides. Therefore, PON1 was defined as a protective factor against atherosclerosis. The aim of this study is to investigate the relation between PON1-related parameters (serum PON1 activity, serum PON1 concentration and PON1 Q192R polymorphism), and the extent and severity of atherosclerosis. Methods: Blood specimens were collected from 130 individuals who had no coronary artery lesions angiographically (control group) and 146 individuals who had angiographically-documented coronary artery disease at several degrees (patient group). PON1 activity was measured using a spectrophotometric method, and PON1 concentration was measured using ELISA. Q192R polymorphism was evaluated using RFLP assay after DNA isolation from samples. Results: Serum PON1 activity was significantly lower in the patient group than controls (126 [42-270] U/mL vs 150 [46-307] U/mL; p<0,05). Serum PON1 concentration was also significantly lower in the patient group than controls (1,44±0,94 mg/dL vs 2,06±0,84 mg/dL, p<0,001). In the patient group, there was a negative correlation between PON1 activity the extent and severity of atherosclerosis (r=-0,270; p=0,002). In both groups, there was no significant difference in the distribution of Q192R polymorphism. Conclusion: It has been concluded that serum PON1 activity is a more significant factor than PON1 genotype in determining the the extent and severity of atherosclerosis. PO24-365
SIMILARITIES OF HEPATIC LIPASE -514C/T AND CHOLESTERYL ESTER TRANSFER PROTEIN I405V POLYMORPHISMS IN BRAZILIAN HYPERALPHALIPOPROTEINEMICS
F. Santiago 1,2 , D. Kaplan 3 , R. Schreiber 2 , J. dos Santos 4 , E. de Faria 1,2,3 . Pathology Departament, FCM, University of Campinas, Sao Paulo; 2 Internal Medicine Departament, FCM, University of Campinas, Sao Paulo; 3 Dyslipidemia Out-patient Service, HC, University of Campinas, Sao Paulo; 4 Lipid Laboratory, University of Sao Paulo Medical School, Ribeirao Preto, Brazil 1 Clinical
Background and aims: Hepatic lipase (HL) and cholesteryl ester transfer protein (CETP) are determinants of HDL concentrations. We compared the effects of HL -514C/T and CETP I405V polymorphisms on lipid and lipoprotein in hyperalphalipoproteinemic (Hyper-A) individuals. Methods: The participants individuals (282-291) were classified as Hyper-A, n= 153, (HDL-C ≥ 68.0 mg/dL) or CTL, n=138, (HDL-C < 68.0 mg/dL). Lipis and lipoproteins were measured using specific enzymatic; isolation of HDL subfractions was performed by ultracentrifugation. HL, lipoprotein lipase (LPL), CETP and phospholipids transfer protein (PLTP) activities were measured using exogenous methods. HL and CETP polymorphisms are determined by PCR follow-up by enzymatic restriction NlaIII (HL-514C/T) and MspI (CETP I405V). Results: HL and LPL activities were lower and higher respectively in HL-514C/T but not CETP in CETP I405V. No changes in PLTP activity were seen in both polymorphisms. In Hyper-A individuals the T allele in -514C/T in relation to CTL, was characterized by higher relative increases of C (14%), HDL2C (33%), HDL3C (18%), HDL3TG (25%) and ApoAI (25%) concentrations. As well the V allele in CETP I405V polymorphism was characterized by higher HDL2C (31%), HDL3C (39%), ApoAI (27%) and TG (6%) concentrations. Only C, TG and HDL3TG variations were not common to both polymorphisms.
77th Congress of the European Atherosclerosis Society, April 26–29, 2008, Istanbul, Turkey
Poster Sessions PO24 Genetic polymorphisms and cardiovascular risk ASSOCIATION OF PLASMA ANGIOTENSINCONVERTING ENZYME ACTIVITY AND GENE POLYMORPHISM IN TUNISIAN PATIENTS AFFECTED WITH MYOCARDIAL INFARCTION
S. Mehri 1,5 , B. Baudin 2 , C. Mahjoub 1 , F. Guemira 3 , M. Rachid 4 , B. Bénéteau-Burnat 2 , S. Ben Arab 1 , M. Hammami 5 . 1 Unité d‘Epidemiologie Génétique et Moleculaire à la Faculté de Médecine de Tunis. Tunisie; 2 Biochimie A, Hopital Saint-Antoine, 184 rue du faubourg Saint-Antoine, 75571 Paris cedex 12, France; 3 Laboratoire de Biochimie et Biologie Moleculaire à l’Hopital Salah Azaiez de Tunis; 4 Services des explorations fonctionnelles Cardiologiques. Hopital La Rabta Tunis. Tunisie; 5 Biochimistry Laboratory UR Background and aims: The Angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism has been studied as a risk factor for acute myocardial infarction (MI) in different populations with conflicting results. Individuals homozygous for the deletion have a higher level of circulating enzyme. The present study is the first report in Tunisia to investigate the association between the ACE gene I/D polymorphism and MI and to examine the relationship between this polymorphism and the serum ACE activity. Material/Methods: ACE I/D polymorphism genotypes were determined by PCR in 101 patients affected with MI and 206 control subjects without history of coronary disease, originated from the same areas. ACE activity was determined by SYNCHRON CX-4 analyser with furylacrylolphenylalanyl- glycyl-glycine as specific substrates. Results: Allele D frequency was 83.2% in patients affected with MI versus 50.7% in control subjects. There was a significant association between D allele and MI (OR =3.55; 95% CI; 2.65-5.33; p <0.001). The mean serum ACE activities was higher in homozygous DD than in I carriers (94.11±47.96 vs 74.31±33.25 and 58.26±13.59 U/L respectively). The serum ACE activities were significantly different between D and I carries in male patients affected with MI. The mean serum ACE activity of D and I was 91.70±46.52 and 67.33±27.14 U/L respectively. Significant ACE activity was found with allele D (p < 0.001). Conclusions: D allele has been associated with increased serum ACE activity. These findings may implicate I/D ACE polymorphism as a genetic marker of MI risk in Tunisian population. PO24-363
EFFECT OF THE RESISTIN -420C>G POLYMORPHISM ON CARDIOVASCULAR DISEASE, DIABETES AND MORTALITY
M.M. Hoffmann 1 , I. Futter 1 , S. Pilz 2 , G. Weihrauch 2 , U. Seelhorst 3 , B.R. Winkelmann 4 , B.O. Boehm 5 , W. Maerz 6 . 1 Clinical Chemistry, University Medical Center, Freiburg, Germany; 2 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, Austria; 3 LURIC Study nonprofit LLC, Freiburg, Germany; 4 Cardiology Group, Frankfurt Sachsenhausen, Germany; 5 Division of Endocrinology and Diabetes, University of Ulm, Germany; 6 Synlab Center of Laboratory Diagnostics, Heidelberg, Germany Resistin is an adipokine involved in the regulation of glucose homeostasis in rodents and probably in humans, too. Apart from this function there is growing evidence of a proatherosclerotic effect of resistin in vascular diseases. A common polymorphism (-420C>G) in the promoter of the resistin gene (RETN) has been described to be associated with resistin plasma levels and susceptibility to type II diabetes. The aim of this study was to investigate the association of this polymorphism with angiographic coronary artery disease, myocardial infarction, type II diabetes, and mortality. Design and results: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study is a prospective study of white subjects who had undergone coronary angiography, including 2553 patients with angiographically documented CAD and 698 individuals in whom CAD had been ruled out by angiography. We could not find any association between a specific promoter genotype of RETN and resistin plasma levels, the risk for CAD, the coronary status, MI or type II diabetes, even after adjustment for traditional risk factors like smoking, gender, and hypertension. Among the 3251 LURIC study participants included in this examination, 622 deaths (19.1%) occurred during a median observation time of 5.4 years. Regardless of whether or not we adjusted for age, sex, and conventional risk factors, the RETN polymorphism showed no association with mortality from all causes or with cardiovascular mortality. Conclusion: An association between the RETN -420C>G polymor-
phism and CAD, MI or type II diabetes at least in Caucasians is unlikely. PO24-364
EVALUATION OF PARAOXONASE-1 GENE POLYMORPHISM AND SERUM PARAOXONASE ACTIVITY AS A CARDIOVASCULAR RISK
T. Bayrak 1 , A. Deniz 2 , L. Tokgozoglu 2 , B. Yavuz 2 , E. Demirpence 1 , A. Bayrak 1 , K. Kilinc 3 , B. Salancı 4 , M. Alikasifoglu 3 , E. Tuncbilek 3 . 1 Hacettepe University Faculty of Medicine Department of Biochemistry; 2 Hacettepe University Faculty of Medicine Department of Cadiology; 3 Hacettepe University Faculty of Medicine Department of Pediatrics, Division of Genetics; 4 Hacettepe University Faculty of Medicine Department of Nucleer Medicine Background: Paraoxonase-1 (PON1) is a high density lipoprotein (HDL)associated enzyme. It has been shown that PON1 protects low density lipoprotein (LDL) particles from oxidative injury by hydrolysing lipoperoxides. Therefore, PON1 was defined as a protective factor against atherosclerosis. The aim of this study is to investigate the relation between PON1-related parameters (serum PON1 activity, serum PON1 concentration and PON1 Q192R polymorphism), and the extent and severity of atherosclerosis. Methods: Blood specimens were collected from 130 individuals who had no coronary artery lesions angiographically (control group) and 146 individuals who had angiographically-documented coronary artery disease at several degrees (patient group). PON1 activity was measured using a spectrophotometric method, and PON1 concentration was measured using ELISA. Q192R polymorphism was evaluated using RFLP assay after DNA isolation from samples. Results: Serum PON1 activity was significantly lower in the patient group than controls (126 [42-270] U/mL vs 150 [46-307] U/mL; p<0,05). Serum PON1 concentration was also significantly lower in the patient group than controls (1,44±0,94 mg/dL vs 2,06±0,84 mg/dL, p<0,001). In the patient group, there was a negative correlation between PON1 activity the extent and severity of atherosclerosis (r=-0,270; p=0,002). In both groups, there was no significant difference in the distribution of Q192R polymorphism. Conclusion: It has been concluded that serum PON1 activity is a more significant factor than PON1 genotype in determining the the extent and severity of atherosclerosis. PO24-365
SIMILARITIES OF HEPATIC LIPASE -514C/T AND CHOLESTERYL ESTER TRANSFER PROTEIN I405V POLYMORPHISMS IN BRAZILIAN HYPERALPHALIPOPROTEINEMICS
F. Santiago 1,2 , D. Kaplan 3 , R. Schreiber 2 , J. dos Santos 4 , E. de Faria 1,2,3 . Pathology Departament, FCM, University of Campinas, Sao Paulo; 2 Internal Medicine Departament, FCM, University of Campinas, Sao Paulo; 3 Dyslipidemia Out-patient Service, HC, University of Campinas, Sao Paulo; 4 Lipid Laboratory, University of Sao Paulo Medical School, Ribeirao Preto, Brazil 1 Clinical
Background and aims: Hepatic lipase (HL) and cholesteryl ester transfer protein (CETP) are determinants of HDL concentrations. We compared the effects of HL -514C/T and CETP I405V polymorphisms on lipid and lipoprotein in hyperalphalipoproteinemic (Hyper-A) individuals. Methods: The participants individuals (282-291) were classified as Hyper-A, n= 153, (HDL-C ≥ 68.0 mg/dL) or CTL, n=138, (HDL-C < 68.0 mg/dL). Lipis and lipoproteins were measured using specific enzymatic; isolation of HDL subfractions was performed by ultracentrifugation. HL, lipoprotein lipase (LPL), CETP and phospholipids transfer protein (PLTP) activities were measured using exogenous methods. HL and CETP polymorphisms are determined by PCR follow-up by enzymatic restriction NlaIII (HL-514C/T) and MspI (CETP I405V). Results: HL and LPL activities were lower and higher respectively in HL-514C/T but not CETP in CETP I405V. No changes in PLTP activity were seen in both polymorphisms. In Hyper-A individuals the T allele in -514C/T in relation to CTL, was characterized by higher relative increases of C (14%), HDL2C (33%), HDL3C (18%), HDL3TG (25%) and ApoAI (25%) concentrations. As well the V allele in CETP I405V polymorphism was characterized by higher HDL2C (31%), HDL3C (39%), ApoAI (27%) and TG (6%) concentrations. Only C, TG and HDL3TG variations were not common to both polymorphisms.
77th Congress of the European Atherosclerosis Society, April 26–29, 2008, Istanbul, Turkey