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ESTROGEN RECEPTOR GENE POLYMORPHISM AND CARDIOVASCULAR DISEASE RISK IN THE FINNISH POPULATION
Poster Sessions PO24 Genetic polymorphisms and cardiovascular risk PO24-358
INTERLEUKIN 18 GENE PROMOTER POLYMORPHISM - A LINK BETWEEN HYPERTENSION AND SUDDEN CARDIAC DEATH THE HELSINKI SUDDEN DEATH STUDY
J.A. Hernesniemi 1 , P.J. Karhunen 2 , R. Rontu 1 , E. Ilveskoski 4 , O. Kajander 2 , S. Goebeler 2 , L.E. Viiri 2 , M. Hurme 3 , T. Lehtimäki 1 . 1 Laboratory of Atherosclerosis Genetics, Tampere University Hospital and the Department of Clinical Chemistry, Medical School, University of Tampere, Tampere, Finland; 2 Department of Forensic Medicine, University of Tampere, Tampere, Finland; 3 Department of Microbiology and Immunology, Tampere University Hospital and the Medical School at the University of Tampere, Tampere, Finland; 4 School of Medicine, University of Tampere and Heart Center, Tampere University Hospital, Tampere, Finland
E. Theodoraki 1 , G. Kolovou 2 , V. Papamikos 1 , A. Limberi 3 , V. Peppes 4 , K. Lazaridis 1 , N. Zakopoulos 4 , G. Dedoussis 1 . 1 Harokopio University, Athens, Greece; 2 Onassis Cardiac Surgery, Athens, Greece; 3 Sotiria Hospital/Athens, Greece; 4 Alexandra Hospital/Athens, Greece Background and aims: To investigate the role of -765G>C polymorphism in cycloxygenase-2 gene in a population of Greek coronary artery disease patients (mean age±SD: 61±10.4) and controls (mean age±SD: 58.63±10.8). Methods: Study subjects were consecutively selected from 3 hospitals around the area of Athens. Cases were subjects presenting first acute coronary syndrome or patients firstly diagnosed with coronary artery disease defined as >50% stenosis in at least one of the three main coronary vessels (63 females, 243 males). The diagnosis of coronary artery disease was set by coronary angiography. Controls were subjects with negative coronary angiography findings or negative stress test that were admitted at the same clinics and the same hospitals as cases (48 females, 71 males). Cases exhibited higher incidence of hyperlipidemia (77.7% vs 64.7%, p=0.009), diabetes (31.5% vs 19.7%, p=0.01) and smoking (76.5% vs 56.1%, p<0.001) than controls. Cases and controls did not differ in respect of family history of myocardial infarction and hypertension incidence. Genotyping was performed by RFLP analysis. Genotypes were available for 217 cases and 96 controls. Results: Genotypes were in hardy-weinberg equilibrium (p=0.97). The frequency of the rare allele was 28%. After performing the chi-square test, genotype frequencies did not differ between cases and controls (p=0.077). After adjustment for various confounders (age, sex, hyperlipidemia, diabetes, hypertension, family history of myocardial infarction, smoking) the effect of the polymorphism on disease occurrence was statistically significant (OR:0.62, 95%CI:0.39-0.99, p=0.046). Conclusions: –765G>C polymorphism in cycloxygenase gene may act as a protective factor against coronary artery disease occurrence. PO24-361
PO24-359
ESTROGEN RECEPTOR GENE POLYMORPHISM AND CARDIOVASCULAR DISEASE RISK IN THE FINNISH POPULATION
T. Kunnas 1,2 , K. Silander 3 , J. Karvanen 4 , M. Valkeapaa 1 , V. Salomaa 5 , L. Peltonen 3 , S. Nikkari 1,2 . 1 Department of Medical Biochemistry, University of Tampere Medical School, University of Tampere, Finland; 2 Research Unit of the Laboratory Centre, Tampere University Hospital, Tampere, Finland; 3 Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland; 4 Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute, Helsinki, Finland; 5 Department of Epidemiology ang Health Promotion, National Public Health Institute, Helsinki, Finland Background and aims: Recent findings suggest that the CC genotype of ESR1 c. 454-397 T >C is associated with higher risk of myocardial infarction (MI) among men. However, results for women on possible genotype dependent risk for cardiovascular disease (CVD) are conflicting. The goal of this study was to investigate the effect of ESR1 genotype on incident CVD events in a prospective cohort among the Finnish population. Results: During the follow up (16 743 person years), 401 incident MIs and 148 ischemic strokes were observed. The CC genotype was tested in Cox proportional hazards models using MI, stroke, and total mortality as end points. The CC genotype contributed to higher risk of MI (HR 1,59, CI 1,1-2,27, P= 0,014), total mortality (HR 1,37, 95% CI 0,97-1,92, P=0,069) and tended to associate with incident stroke (HR 1,35, 95% CI 0,80-2,27, P=0,258). In women, the minor genotype CC contributed to the risk of MI (HR 2,50, 95% CI 1,06-5,88, p=0,036), stroke (HR 2,63, 95% CI 1,04-6,67, P=0,042) and total mortality (HR 1,92, 95% CI 1,00-3,70,P=0,051). In men, the rare genotype tended to associate with MI (HR 1,47, 95% CI 0,98-2,22, P=0,064), but not with ischemic stroke or total mortality. Conclusion: This population based study suggests that the rare genotype of the ESR1 gene (CC) contributes to a higher risk of MI, stroke and total mortality among women and a higher risk of MI among men, compared to those who have dominant T-allele of the gene.
CYCLOXYGENASE-2 -765G>C POLYMORPHISM MAY BE A PROTECTIVE FACTOR AGAINST CORONARY ARTERY DISEASE IN THE GREEK POPULATION
APOLIPOPROTEIN E POLYMORPHISM AND CORONARY HEART DISEASE AND TYPE 2 DIABETESND TYPE 2 DIABETES
S. Liu, X. Zhou, Y. Xiong, Y. Yang, C. Wang, X. Qu, Y. Xie, H. Hu, Z. Pang. Gene diagnosis center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China Backgroud and aims: To further investigate the association between ApoE genetic polymorphism, plasma lipid levels, fasting blood glucose (FBG) and coronary heart disease (CHD) and type 2 diabetes (T2D). Methods: PCR- RFLP, multiplex amplification refractory mutation system and PCR- single strand conformation polymorphism (SSCP) methods and DNA sequencing were used to genotype 203 cases of CHD, 316 cases of T2D and 1892 healthy controls. FBG and plasma lipids were measured by usual methods. Results: Compared with the controls, plasma HDL-C and ApoAI levels in the CHD group were significantly lower; Plasma TC level in the T2D group was significantly higher; blood pressure, plasma TG, LDL-C, ApoB, Lp (a) and FBG levels were significantly higher in both two group; Significant differences were found between the CHD group (χ2=13.816, P=0.008), T2D group (χ2=11.448, P=0.022) and the control group for the frequencies of ApoE genotype. The distribution of ε3/4 was higher (26.6% vs. 17.0%) in the CHD group, ε4/4 was higher (4.1% VS 1.2%) in the T2D group, and 2 cases of ε3/3 with Arg 150 His mutation were firstly reported in Chinese T2D. Conclusion: The results suggested that ApoE ε3/4 andε4/4 were the susceptibility genotypes for CHD and T2D, respectively. Blood pressure and plasma lipids could be used for diagnosis of the two diseases.
77th Congress of the European Atherosclerosis Society, April 26–29, 2008, Istanbul, Turkey
POSTER SESSIONS
Background and aims: Interleukin 18 (IL-18) gene has a single nucleotide promoter region (-137) G-to-C polymorphism (rs187238) which leads to attenuated transcriptional activity of the gene and to lower production of pro-atherogenic IL-18. The C allele of this polymorphism is associated with lower risk for Sudden Cardiac Death (SCD) due to Coronary Heart Disease (CHD). We wanted to examine that would this polymorphism modify the risk of such deaths by altering the effect of environmental risk factors for SCD (hypertension, diabetes, smoking, alcohol consumption and BMI). Methods: TaqMan 5’ nuclease assay was used to genotype the study population of the Helsinki Sudden Death study, comprising medicolegal autopsies of 700 men. Logistic regression analysis, adjusted with common risk factors, was used to calculate the significance of interactions and to compare the effect of risk factors among IL-18 genotype groups. Results: The genotyping was successful in 663 (94.7%) cases. The genotype frequencies in the order of GG-GC-CC were: 359 (54.1%), 261 (39.4%) and 43 (6.5%). IL-18 genotype significantly interacted only with hypertension on the occurrence of CHD related SCD (p=0.011). Among GG homozygotes hypertension was a major risk factor for SCD due to CHD (OR 3.75 with 95% CI 1.78 to 7.91, p<0.001). Among the C allele carriers hypertension was not a significant risk factor for SCD due to CHD (OR 0.78, 95% CI 0.32 to 1.91, p=0.583). Conclusions: IL-18 gene promoter polymorphism (rs187238) modulates the effect of hypertension on the risk for SCD due to CHD.
PO24-360
105
INTERLEUKIN 18 GENE PROMOTER POLYMORPHISM - A LINK BETWEEN HYPERTENSION AND SUDDEN CARDIAC DEATH THE HELSINKI SUDDEN DEATH STUDY
J.A. Hernesniemi 1 , P.J. Karhunen 2 , R. Rontu 1 , E. Ilveskoski 4 , O. Kajander 2 , S. Goebeler 2 , L.E. Viiri 2 , M. Hurme 3 , T. Lehtimäki 1 . 1 Laboratory of Atherosclerosis Genetics, Tampere University Hospital and the Department of Clinical Chemistry, Medical School, University of Tampere, Tampere, Finland; 2 Department of Forensic Medicine, University of Tampere, Tampere, Finland; 3 Department of Microbiology and Immunology, Tampere University Hospital and the Medical School at the University of Tampere, Tampere, Finland; 4 School of Medicine, University of Tampere and Heart Center, Tampere University Hospital, Tampere, Finland
E. Theodoraki 1 , G. Kolovou 2 , V. Papamikos 1 , A. Limberi 3 , V. Peppes 4 , K. Lazaridis 1 , N. Zakopoulos 4 , G. Dedoussis 1 . 1 Harokopio University, Athens, Greece; 2 Onassis Cardiac Surgery, Athens, Greece; 3 Sotiria Hospital/Athens, Greece; 4 Alexandra Hospital/Athens, Greece Background and aims: To investigate the role of -765G>C polymorphism in cycloxygenase-2 gene in a population of Greek coronary artery disease patients (mean age±SD: 61±10.4) and controls (mean age±SD: 58.63±10.8). Methods: Study subjects were consecutively selected from 3 hospitals around the area of Athens. Cases were subjects presenting first acute coronary syndrome or patients firstly diagnosed with coronary artery disease defined as >50% stenosis in at least one of the three main coronary vessels (63 females, 243 males). The diagnosis of coronary artery disease was set by coronary angiography. Controls were subjects with negative coronary angiography findings or negative stress test that were admitted at the same clinics and the same hospitals as cases (48 females, 71 males). Cases exhibited higher incidence of hyperlipidemia (77.7% vs 64.7%, p=0.009), diabetes (31.5% vs 19.7%, p=0.01) and smoking (76.5% vs 56.1%, p<0.001) than controls. Cases and controls did not differ in respect of family history of myocardial infarction and hypertension incidence. Genotyping was performed by RFLP analysis. Genotypes were available for 217 cases and 96 controls. Results: Genotypes were in hardy-weinberg equilibrium (p=0.97). The frequency of the rare allele was 28%. After performing the chi-square test, genotype frequencies did not differ between cases and controls (p=0.077). After adjustment for various confounders (age, sex, hyperlipidemia, diabetes, hypertension, family history of myocardial infarction, smoking) the effect of the polymorphism on disease occurrence was statistically significant (OR:0.62, 95%CI:0.39-0.99, p=0.046). Conclusions: –765G>C polymorphism in cycloxygenase gene may act as a protective factor against coronary artery disease occurrence. PO24-361
PO24-359
ESTROGEN RECEPTOR GENE POLYMORPHISM AND CARDIOVASCULAR DISEASE RISK IN THE FINNISH POPULATION
T. Kunnas 1,2 , K. Silander 3 , J. Karvanen 4 , M. Valkeapaa 1 , V. Salomaa 5 , L. Peltonen 3 , S. Nikkari 1,2 . 1 Department of Medical Biochemistry, University of Tampere Medical School, University of Tampere, Finland; 2 Research Unit of the Laboratory Centre, Tampere University Hospital, Tampere, Finland; 3 Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland; 4 Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute, Helsinki, Finland; 5 Department of Epidemiology ang Health Promotion, National Public Health Institute, Helsinki, Finland Background and aims: Recent findings suggest that the CC genotype of ESR1 c. 454-397 T >C is associated with higher risk of myocardial infarction (MI) among men. However, results for women on possible genotype dependent risk for cardiovascular disease (CVD) are conflicting. The goal of this study was to investigate the effect of ESR1 genotype on incident CVD events in a prospective cohort among the Finnish population. Results: During the follow up (16 743 person years), 401 incident MIs and 148 ischemic strokes were observed. The CC genotype was tested in Cox proportional hazards models using MI, stroke, and total mortality as end points. The CC genotype contributed to higher risk of MI (HR 1,59, CI 1,1-2,27, P= 0,014), total mortality (HR 1,37, 95% CI 0,97-1,92, P=0,069) and tended to associate with incident stroke (HR 1,35, 95% CI 0,80-2,27, P=0,258). In women, the minor genotype CC contributed to the risk of MI (HR 2,50, 95% CI 1,06-5,88, p=0,036), stroke (HR 2,63, 95% CI 1,04-6,67, P=0,042) and total mortality (HR 1,92, 95% CI 1,00-3,70,P=0,051). In men, the rare genotype tended to associate with MI (HR 1,47, 95% CI 0,98-2,22, P=0,064), but not with ischemic stroke or total mortality. Conclusion: This population based study suggests that the rare genotype of the ESR1 gene (CC) contributes to a higher risk of MI, stroke and total mortality among women and a higher risk of MI among men, compared to those who have dominant T-allele of the gene.
CYCLOXYGENASE-2 -765G>C POLYMORPHISM MAY BE A PROTECTIVE FACTOR AGAINST CORONARY ARTERY DISEASE IN THE GREEK POPULATION
APOLIPOPROTEIN E POLYMORPHISM AND CORONARY HEART DISEASE AND TYPE 2 DIABETESND TYPE 2 DIABETES
S. Liu, X. Zhou, Y. Xiong, Y. Yang, C. Wang, X. Qu, Y. Xie, H. Hu, Z. Pang. Gene diagnosis center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China Backgroud and aims: To further investigate the association between ApoE genetic polymorphism, plasma lipid levels, fasting blood glucose (FBG) and coronary heart disease (CHD) and type 2 diabetes (T2D). Methods: PCR- RFLP, multiplex amplification refractory mutation system and PCR- single strand conformation polymorphism (SSCP) methods and DNA sequencing were used to genotype 203 cases of CHD, 316 cases of T2D and 1892 healthy controls. FBG and plasma lipids were measured by usual methods. Results: Compared with the controls, plasma HDL-C and ApoAI levels in the CHD group were significantly lower; Plasma TC level in the T2D group was significantly higher; blood pressure, plasma TG, LDL-C, ApoB, Lp (a) and FBG levels were significantly higher in both two group; Significant differences were found between the CHD group (χ2=13.816, P=0.008), T2D group (χ2=11.448, P=0.022) and the control group for the frequencies of ApoE genotype. The distribution of ε3/4 was higher (26.6% vs. 17.0%) in the CHD group, ε4/4 was higher (4.1% VS 1.2%) in the T2D group, and 2 cases of ε3/3 with Arg 150 His mutation were firstly reported in Chinese T2D. Conclusion: The results suggested that ApoE ε3/4 andε4/4 were the susceptibility genotypes for CHD and T2D, respectively. Blood pressure and plasma lipids could be used for diagnosis of the two diseases.
77th Congress of the European Atherosclerosis Society, April 26–29, 2008, Istanbul, Turkey
POSTER SESSIONS
Background and aims: Interleukin 18 (IL-18) gene has a single nucleotide promoter region (-137) G-to-C polymorphism (rs187238) which leads to attenuated transcriptional activity of the gene and to lower production of pro-atherogenic IL-18. The C allele of this polymorphism is associated with lower risk for Sudden Cardiac Death (SCD) due to Coronary Heart Disease (CHD). We wanted to examine that would this polymorphism modify the risk of such deaths by altering the effect of environmental risk factors for SCD (hypertension, diabetes, smoking, alcohol consumption and BMI). Methods: TaqMan 5’ nuclease assay was used to genotype the study population of the Helsinki Sudden Death study, comprising medicolegal autopsies of 700 men. Logistic regression analysis, adjusted with common risk factors, was used to calculate the significance of interactions and to compare the effect of risk factors among IL-18 genotype groups. Results: The genotyping was successful in 663 (94.7%) cases. The genotype frequencies in the order of GG-GC-CC were: 359 (54.1%), 261 (39.4%) and 43 (6.5%). IL-18 genotype significantly interacted only with hypertension on the occurrence of CHD related SCD (p=0.011). Among GG homozygotes hypertension was a major risk factor for SCD due to CHD (OR 3.75 with 95% CI 1.78 to 7.91, p<0.001). Among the C allele carriers hypertension was not a significant risk factor for SCD due to CHD (OR 0.78, 95% CI 0.32 to 1.91, p=0.583). Conclusions: IL-18 gene promoter polymorphism (rs187238) modulates the effect of hypertension on the risk for SCD due to CHD.
PO24-360
105