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THE ASSOCIATION BETWEEN THE IL6-6331T > C POLYMORPHISM AND METABOLIC SYNDROME IN THE TURKISH ADULT RISK FACTOR (TARF) STUDY
110
Poster Sessions PO24 Genetic polymorphisms and cardiovascular risk
showed an opposite effect in terms of CHD risk with these two SNPs. The higher CHD risk in the U3_A>G SNP may be related to the presence of higher TG levels. Our data indicate that genetic variation at the LDLR gene loci can affect total-C, LDL-C and TG levels and CHD risk.
PO24-381
ESTROGEN RECEPTOR BETA GENE POLYMORPHISM IS ASSOCIATED WITH VASCULAR DEMENTIA IN WOMEN
R. Dresner-pollak 1 , T. Kinar 3 , Y. Friedlander 4 , A. Rokach 5 , A. Pollak 2 . Hadassah-Hebrew University Medical Center,Jerusalem,Israel; 2 Heart Institute, Hadassah-Hebrew University Medical Center,Jerusalem,Israel; 3 Hadassah-Hebrew University School of Medicine, Jerusalem,Israel; 4 Hadassah-Hebrew University School of Public Health, Jerusalem,Israel; 5 Pulmonary Service,Hadassah-Hebrew University Medical Center,Jerusalem,Israel 1 Endocrinology,
PO24-379
THE ASSOCIATION BETWEEN THE IL6-6331T>C POLYMORPHISM AND METABOLIC SYNDROME IN THE TURKISH ADULT RISK FACTOR (TARF) STUDY
M. Poda 1 , F. Guclu-Geyik 1 , A. Yuzbasiogullari 1 , G. Can 2 , A. Onat 3 , S. Humphries 4 , N. Erginel-Unaltuna 1 . 1 Genetics Dept., DETAE, Istanbul University,Istanbul,Turkey; 2 Public Health Dept, Cerrahpasa Med. Faculty, Istanbul University,Istanbul,Turkey; 3 Turkish Cardiology Association,Istanbul,Turkey; 4 Centre for Cardiovascular Genetics, BHF Laboratories, Royal Free and University College London Medical School, London, UK Background and aims: Interleukin-6 (IL-6) is a pleiotropic cytokine, which has been linked to age-related metabolic disturbances such as metabolic syndrome (MS) and diabetes. In a large representative cohort of Turkey (TARF study), we have examined the effect of the IL6 -6331T>C gene polymorphism on MS and its components. Methods: Genotyping was performed using the TaqMan 7900HT in 1912 adult individuals (mean age 55.7±11.7; 49.0% male). Results: Overall, genotype frequencies were TT=55.7%, TC=37.0% and CC=7.3% and were as expected for Hardy-Weinberg Equilibrium. 46.1% of TT subjects had metabolic syndrome compared to 51.6% of TC subjects (p<0.05) The association of MS with TC genotype was confirmed by regression analysis using age and sex as covariates (OR=1.23; 95% CI=1.01-1.4; p=0.04). This genotype was also associated with increased waist circumference (p<0.03) in the whole group, and a higher waist to hip ratio (WHR) was observed in TC female subjects (p<0.04). In parallel to this, mean glucose levels of TT male subjects were significantly lower (P=0.05). Both male and female TT subjects had significantly higher levels of Lp(a) (p=0,02), and this effect was stronger in males (p<0.04). Conclusions: The C allele of the IL6 -6331TC genotype is associated with several componants of the metabolic syndrome and with risk of MS itself. This highlights the key role of inflammation and of IL-6 levels in the etiology of MS. PO24-380
STUDY OF INFLAMMATORY CYTOKINES AND ENOS GENE POLYMORPHISM IN PREGNANCY INDUCED HYPERTENSION
J. Bhattacharjee 1 , A. Singh 1 , D. Sharma 1 , R. Chitra 2 . 1 Department of Biochemistry, Lady Hardinge Medical College and Associated Hospitals,New Delhi,Delhi,India; 2 Department of Obs & Gyne, Lady Hardinge Medical College, New Delhi,Delhi, India Background: Alteration of Nitric Oxide (NO) production from endothelial cells is implicated in the pathogenesis of Pregnancy induced hypertension (PIH). G894T mutation of eNOS gene is associated with reduced endothelium dependent vasodilatation. Endothelial dysfunction in turn causes abnormal immune activation, releasing inflammatory cytokines. Objectives: The study was aimed to explore pathophysiological role of NO, inflammatory cytokines levels and eNOS gene polymorphism in PIH. Methods: The study included 50 PIH cases and 50 controls of matched healthy pregnant women. NO level was estimated spectrophotometrically and inflammatory cytokines by ELISA. Study of eNOS gene polymorphism was carried out by DNA extraction and screening for RFLP. Results: The difference in level of NO, TNFα, IL-6and IL-2 between the two groups was significant. Serum NO and IL-6 have showed significant –ve correlation in study group. In genotype study, the frequency of G allele was 97% in study group and 98% in control group. The frequency of T allele was 3% in study group and 2% in control group. The difference between the two was not significant. Conclusion: Our study showed significantly lower levels of serum nitric oxide levels in study group. Levels of inflammatory Th-1 cytokines were found to be significantly higher in PIH. Significant negative correlation between levels of NO and IL-6 suggests that an endothelium dependent NO-cGMP mediated relaxation pathway is inhibited in systemic vessels of patients having PIH. Glu298Asp gene polymorphism was not found associated with PIH but subjects having GT genotypes have got impaired NO production.
Background and Aims: Alzheimer’s disease (AD) and vascular dementia (VD) are the most common causes of dementia. The reduction in estrogen levels after menopause has been suggested as an important contributor to the development of dementia in women. However, large clinical trials failed to demonstrate a beneficial effect of estrogen replacement therapy in the prevention of dementia or cerebrovascular disease. We investigated weather sequence variants in the estrogen receptor alpha (ESR1) and beta (ESR2) genes are associated with AD or VD in women, and thus may attenuate the effects of estrogens. Methods: 246 elderly women (118 AD, age 83±7, 60 VD, age 82±6, and 68 cognitively intact, age 81±7) were genotyped for APOE4 ε, the ESR1 polymorphisms: C.454-397T>C (PvuII), c.454-351 A>G (XbaI) and the (TA) repeat polymorphism in the promoter region of the gene, and the 1730 A>G (AluI) polymorphism in the ESR2 gene. The diagnosis of AD and VD was based on the DSM-IV and the NINCDS-ADRDA criteria, and cognitively intact subjects were defined based on Folstein Mini-Mental State Exam score above 23. The association between genotypes and AD and VD was determined by logistic regression analysis assuming an additive model, and was corrected for age and ethnicity. ESR1 Haplotype frequency was determined by PHASE 2.0. Results: The ESR2 AluI polymorphism was associated with VD (OR 1.72, 95% CI: 1-2.95). No association was found with ESR1 genotypes or haplotypes. Conclusion: ESR2 gene polymorphism is associated with VD in elderly women, and may help identify women at increased risk for VD. PO24-382
A COMMON VARIANT IN THE FTO GENE IS ASSOCIATED WITH BMI IN MALES AND POSTMENOPAUSAL, BUT NOT IN PREMENOPAUSAL FEMALES
J. Hubacek 1,2 , R. Bohuslavova 1 , L. Kuthanova 1 , J. Pitha 1,2 , V. Adamkova 1 , R. Poledne 1,2 . 1 Institute for Clinical and Experimental Medicine, Prague, Czech Republic; 2 Cardiovascular Research Centre, Prague, Czech Republic Background and aims: Obesity is the serious health problem worldwide and is associated with increased risk of heart disease, stroke and type 2 diabetes mellitus. Obesity has an important genetic component estimated on 40-60%. FTO (“fat mass and obesity related gene”, exact function unknown) gene and its variants has been recently associated with the BMI determination in west European populations. We have analyzed the association between the FTO gene variant rs17817449 and BMI in middle European - Slavic population. Methods: FTO variant rs17817449 (G>T) was analyzed by PCR-RFLP in three groups of adults – in 1191 males and 1368 females selected according the MONICA protocol, and in 839 representatively selected females with FSH-determined menopausal status (FSH for premenopausal status < 40U/L). ANOVA was used for statistical analysis. Results: Genotype frequencies in Slavic population were similar to the previously described west European populations (GG – 18%; GT – 50%; TT – 32%). FTO rs17817449 variant was significantly associated with BMI (kg/m2 ) in MONICA-males (GG – 28.7±3.7; GT – 28.3±4.1; TT – 27.8±3.9; P=0.014) but not in MONICA-females (data not shown). In females, FTO affects the BMI in postmenopausal (N=485; GG – 27.5±6.2; GT – 25.5±4.6; TT – 25.7±4.8; P=0.035) but not in premenopausal females (N=354; GG – 25.8±4.6; GT – 26.1±4.8; TT – 25.8±4.5; P=n.s.) Conclusions: FTO variants have an effect on BMI in males and postmenopausal females, but not in premenopausal females. Supported by research project No. 1M0510 (Ministry of Education, Youth and Sports of the Czech Republic).
77th Congress of the European Atherosclerosis Society, April 26–29, 2008, Istanbul, Turkey
Poster Sessions PO24 Genetic polymorphisms and cardiovascular risk
showed an opposite effect in terms of CHD risk with these two SNPs. The higher CHD risk in the U3_A>G SNP may be related to the presence of higher TG levels. Our data indicate that genetic variation at the LDLR gene loci can affect total-C, LDL-C and TG levels and CHD risk.
PO24-381
ESTROGEN RECEPTOR BETA GENE POLYMORPHISM IS ASSOCIATED WITH VASCULAR DEMENTIA IN WOMEN
R. Dresner-pollak 1 , T. Kinar 3 , Y. Friedlander 4 , A. Rokach 5 , A. Pollak 2 . Hadassah-Hebrew University Medical Center,Jerusalem,Israel; 2 Heart Institute, Hadassah-Hebrew University Medical Center,Jerusalem,Israel; 3 Hadassah-Hebrew University School of Medicine, Jerusalem,Israel; 4 Hadassah-Hebrew University School of Public Health, Jerusalem,Israel; 5 Pulmonary Service,Hadassah-Hebrew University Medical Center,Jerusalem,Israel 1 Endocrinology,
PO24-379
THE ASSOCIATION BETWEEN THE IL6-6331T>C POLYMORPHISM AND METABOLIC SYNDROME IN THE TURKISH ADULT RISK FACTOR (TARF) STUDY
M. Poda 1 , F. Guclu-Geyik 1 , A. Yuzbasiogullari 1 , G. Can 2 , A. Onat 3 , S. Humphries 4 , N. Erginel-Unaltuna 1 . 1 Genetics Dept., DETAE, Istanbul University,Istanbul,Turkey; 2 Public Health Dept, Cerrahpasa Med. Faculty, Istanbul University,Istanbul,Turkey; 3 Turkish Cardiology Association,Istanbul,Turkey; 4 Centre for Cardiovascular Genetics, BHF Laboratories, Royal Free and University College London Medical School, London, UK Background and aims: Interleukin-6 (IL-6) is a pleiotropic cytokine, which has been linked to age-related metabolic disturbances such as metabolic syndrome (MS) and diabetes. In a large representative cohort of Turkey (TARF study), we have examined the effect of the IL6 -6331T>C gene polymorphism on MS and its components. Methods: Genotyping was performed using the TaqMan 7900HT in 1912 adult individuals (mean age 55.7±11.7; 49.0% male). Results: Overall, genotype frequencies were TT=55.7%, TC=37.0% and CC=7.3% and were as expected for Hardy-Weinberg Equilibrium. 46.1% of TT subjects had metabolic syndrome compared to 51.6% of TC subjects (p<0.05) The association of MS with TC genotype was confirmed by regression analysis using age and sex as covariates (OR=1.23; 95% CI=1.01-1.4; p=0.04). This genotype was also associated with increased waist circumference (p<0.03) in the whole group, and a higher waist to hip ratio (WHR) was observed in TC female subjects (p<0.04). In parallel to this, mean glucose levels of TT male subjects were significantly lower (P=0.05). Both male and female TT subjects had significantly higher levels of Lp(a) (p=0,02), and this effect was stronger in males (p<0.04). Conclusions: The C allele of the IL6 -6331TC genotype is associated with several componants of the metabolic syndrome and with risk of MS itself. This highlights the key role of inflammation and of IL-6 levels in the etiology of MS. PO24-380
STUDY OF INFLAMMATORY CYTOKINES AND ENOS GENE POLYMORPHISM IN PREGNANCY INDUCED HYPERTENSION
J. Bhattacharjee 1 , A. Singh 1 , D. Sharma 1 , R. Chitra 2 . 1 Department of Biochemistry, Lady Hardinge Medical College and Associated Hospitals,New Delhi,Delhi,India; 2 Department of Obs & Gyne, Lady Hardinge Medical College, New Delhi,Delhi, India Background: Alteration of Nitric Oxide (NO) production from endothelial cells is implicated in the pathogenesis of Pregnancy induced hypertension (PIH). G894T mutation of eNOS gene is associated with reduced endothelium dependent vasodilatation. Endothelial dysfunction in turn causes abnormal immune activation, releasing inflammatory cytokines. Objectives: The study was aimed to explore pathophysiological role of NO, inflammatory cytokines levels and eNOS gene polymorphism in PIH. Methods: The study included 50 PIH cases and 50 controls of matched healthy pregnant women. NO level was estimated spectrophotometrically and inflammatory cytokines by ELISA. Study of eNOS gene polymorphism was carried out by DNA extraction and screening for RFLP. Results: The difference in level of NO, TNFα, IL-6and IL-2 between the two groups was significant. Serum NO and IL-6 have showed significant –ve correlation in study group. In genotype study, the frequency of G allele was 97% in study group and 98% in control group. The frequency of T allele was 3% in study group and 2% in control group. The difference between the two was not significant. Conclusion: Our study showed significantly lower levels of serum nitric oxide levels in study group. Levels of inflammatory Th-1 cytokines were found to be significantly higher in PIH. Significant negative correlation between levels of NO and IL-6 suggests that an endothelium dependent NO-cGMP mediated relaxation pathway is inhibited in systemic vessels of patients having PIH. Glu298Asp gene polymorphism was not found associated with PIH but subjects having GT genotypes have got impaired NO production.
Background and Aims: Alzheimer’s disease (AD) and vascular dementia (VD) are the most common causes of dementia. The reduction in estrogen levels after menopause has been suggested as an important contributor to the development of dementia in women. However, large clinical trials failed to demonstrate a beneficial effect of estrogen replacement therapy in the prevention of dementia or cerebrovascular disease. We investigated weather sequence variants in the estrogen receptor alpha (ESR1) and beta (ESR2) genes are associated with AD or VD in women, and thus may attenuate the effects of estrogens. Methods: 246 elderly women (118 AD, age 83±7, 60 VD, age 82±6, and 68 cognitively intact, age 81±7) were genotyped for APOE4 ε, the ESR1 polymorphisms: C.454-397T>C (PvuII), c.454-351 A>G (XbaI) and the (TA) repeat polymorphism in the promoter region of the gene, and the 1730 A>G (AluI) polymorphism in the ESR2 gene. The diagnosis of AD and VD was based on the DSM-IV and the NINCDS-ADRDA criteria, and cognitively intact subjects were defined based on Folstein Mini-Mental State Exam score above 23. The association between genotypes and AD and VD was determined by logistic regression analysis assuming an additive model, and was corrected for age and ethnicity. ESR1 Haplotype frequency was determined by PHASE 2.0. Results: The ESR2 AluI polymorphism was associated with VD (OR 1.72, 95% CI: 1-2.95). No association was found with ESR1 genotypes or haplotypes. Conclusion: ESR2 gene polymorphism is associated with VD in elderly women, and may help identify women at increased risk for VD. PO24-382
A COMMON VARIANT IN THE FTO GENE IS ASSOCIATED WITH BMI IN MALES AND POSTMENOPAUSAL, BUT NOT IN PREMENOPAUSAL FEMALES
J. Hubacek 1,2 , R. Bohuslavova 1 , L. Kuthanova 1 , J. Pitha 1,2 , V. Adamkova 1 , R. Poledne 1,2 . 1 Institute for Clinical and Experimental Medicine, Prague, Czech Republic; 2 Cardiovascular Research Centre, Prague, Czech Republic Background and aims: Obesity is the serious health problem worldwide and is associated with increased risk of heart disease, stroke and type 2 diabetes mellitus. Obesity has an important genetic component estimated on 40-60%. FTO (“fat mass and obesity related gene”, exact function unknown) gene and its variants has been recently associated with the BMI determination in west European populations. We have analyzed the association between the FTO gene variant rs17817449 and BMI in middle European - Slavic population. Methods: FTO variant rs17817449 (G>T) was analyzed by PCR-RFLP in three groups of adults – in 1191 males and 1368 females selected according the MONICA protocol, and in 839 representatively selected females with FSH-determined menopausal status (FSH for premenopausal status < 40U/L). ANOVA was used for statistical analysis. Results: Genotype frequencies in Slavic population were similar to the previously described west European populations (GG – 18%; GT – 50%; TT – 32%). FTO rs17817449 variant was significantly associated with BMI (kg/m2 ) in MONICA-males (GG – 28.7±3.7; GT – 28.3±4.1; TT – 27.8±3.9; P=0.014) but not in MONICA-females (data not shown). In females, FTO affects the BMI in postmenopausal (N=485; GG – 27.5±6.2; GT – 25.5±4.6; TT – 25.7±4.8; P=0.035) but not in premenopausal females (N=354; GG – 25.8±4.6; GT – 26.1±4.8; TT – 25.8±4.5; P=n.s.) Conclusions: FTO variants have an effect on BMI in males and postmenopausal females, but not in premenopausal females. Supported by research project No. 1M0510 (Ministry of Education, Youth and Sports of the Czech Republic).
77th Congress of the European Atherosclerosis Society, April 26–29, 2008, Istanbul, Turkey