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USF1 GENE IS INVOLVED IN THE REGULATION OF HUMAN LONGEVITY
Poster Sessions PO24 Genetic polymorphisms and cardiovascular risk PO24-350
USF1 GENE IS INVOLVED IN THE REGULATION OF HUMAN LONGEVITY
B. Ozsait 1,2,5 , E. Komurcu-Bayrak 1,2,5 , M. Jylha 3 , M. Perola 4 , K. Kristiansson 4 , N. Mononen 1,2 , M. Hurme 1,2 , R. Laaksonen 1,2 , A. Hervonen 3 , N. Erginel-Unaltuna 5 , P. Karhunen 1,2 , T. Lehtimaki 1,2 . 1 University of Tampere Medical School, Tampere, Finland; 2 The Laboratory Centre, Tampere University Hospital, Tampere, Finland; 3 Tampere School of Public Health, Tampere, Finland; 4 Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland; 5 Department of Genetics, Institute for Medical Research, Istanbul University, Istanbul, Turkey
PO24-351
ASSOCIATION OF LIPOPROTEIN LIPASE GENE MARKER WITH LIPID PROFILE IN ESSENTIAL HYPERTENSION
B. Susleyici Duman 1 , C. Ciftci 2 , P. Cagatay 3 . 1 Department of Medical Biology and Genetics, Istanbul Science University Medical Faculty, Istanbul, Turkey; 2 Department of Cardiology, Istanbul Science University Medical Faculty, Florence Nightingale Hospital, Istanbul, Turkey; 3 Department of Biostatistics, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey Background and aims: Lipoprotein lipase (LPL) gene involved in triglycerides metabolism, may be involved in the genetic component of the development of hypertension. In this case-control study, we aimed to determine the association between essential hypertension (EH) and LPL PvuII genotypes as a result of C497→T transition. Additionally, PvuII genotypes were investigated for their association with serum lipids. Methods: The study group was composed of 50 individuals with EH and 51 normotensive controls. PCR-RFLP was used to determine the PvuII variation of the LPL gene. Results: The PvuII C/T, C/C and T/T genotype frequencies were respectively 34%, 24%, 42% in EH; 39.2%, 37.3%, 23.5% in controls. The frequencies of PvuII genotypes did not differ significantly between case and controls. LPL PvuII polymorphism was found to be effective over HDL-cholesterol and total-cholesterol. Total-cholesterol was found to be the higher in mutant (TT) genotype in comparison to CT and CC carriers in both patients and controls. In controls, the highest and lowest HDL-cholesterol levels were respectively found in CC and CT genotypes. Whereas the EH patients with CT had the lowest HDL-cholesterol compared to CC and TT genotypes. With logistic regression analysis LPL gene PvuII genotypes were not found to be associated with EH. Conclusions: Our study failed to reveal an association of LPL PvuII locus with hypertension. However, significant differences were found in HDL- and total-cholesterol levels among PvuII genotypes in EH patients. Larger population-based studies are needed to understand the exact role of LPL gene locus in causing EH.
A COMMON POLYMORPHISM IN THE ATP-BINDING CASSETTE PROTEIN A1 GENE AND HDL-C METABOLISM IN IRAN
S. Halalkhor 1 , S.A. Mesbah-Namin 1 , M.S. Daneshpour 2 , P. Eshragi 2 , M. Hedayati 2 , F. Azizi 2 . 1 Clinical Biochemistry,School of Medical Sciences,Tarbiat Modares University, Tehran, IRAN; 2 Research Institute for Endocrine Sciences, Shaheed Beheshti University of Medical Sciences, Tehran, IRAN Background and aims: Low plasma HDL-C is associated with an increased risk of coronary artery disease (CAD). The ATP-binding cassette transporter-1 (ABCA1) mediates cholesterol efflux and genotypic variation of ABCA1 common polymorphism frequency and its association with HDL-C level in Iranian population. Methods: 700 subjects were selected randomly from the Tehran Lipid Glucose Study center. HDL-C, in ABCA1 and may impact reverse cholesterol transport and influence cardiovascular disease (CVD) risk. The aim of this study was determination LDL-C, TG and FBS levels were determined. Genomic DNA was extracted and the region contains 1051 G/A (R219K) in Exon 7 was amplified by PCR and the polymorphism was reveled by XagI as restriction enzyme in RFLP. Results: The frequency of R219K variant was 63% in the population. HDL-C level showed association with the common polymorphism of ABCA1 gene. Conclusions: The obtained data suggest that the common variation in ABCA1 significantly influences plasma HDL-C levels. PO24-353
AN ASSOCIATION BETWEEN HOMOCYSTEINE, MTHFR C677T GENE POLYMORPHISM, THIOLACTONASE ACTIVITY AND LIPID PARAMETERS IN TUNISIAN CORONARY HEART DISEASE PATIENTS
N. Koubaa 1 , A. Nakbi 1 , K. Ben Hamda 2 , S. Hammami 3 , M. Smaoui 1 , N. Attia 1 , M. Hammami 1 . 1 Laboratory of Biochemistry, UR “Human Nutrition and Metabolic Disorders” Faculty of Medicine, Monastir, Tunisia; 2 Department Cardiology, CHU F.Bourguiba, Monastir, Tunisia; 3 Department of Internal Medicine, CHU F.Bourguiba, Monastir, Tunisia Background and aims: Hyperhomocysteinemia (HHcy) is an important, independent risk factor for atherosclerosis and thrombotic disease. HHcy generates oxidative stress and induces vascular damage. We aimed to evaluate tHcy levels according to CAD severity and their association with MTHFR C677T gene polymorphism, thiolactonase activity (HTLase) and some lipid parameters. Methods: Consecutive 93 patients (60.7±11 years) with angiographically documented CHD were involved and classified into 3 groups according to the severity of CAD manifestations: stable orunstable angina pectoris, (SAP, n= 15; UAP, n= 42) and acute myocardial infarction (AMI, n= 36). Biochemical analysis was performed using validated methods as previously described (Koubaa et al. Clinical Biochemistry 2007). Results: AMI patients showed higher tHcy levels as compared with the SAP ones (17.4 vs. 14 µmol/l, p=0.06) associated with lower HTLase (359.7 vs. 477.9 U/ml, p=0.038). Furthermore, AMI patients exhibited significantly lower HDL-C levels. In the AMI group, tHcy levels were negatively correlated with HTLase activity (r = -0.754, p = 0.00). A positive correlation was found between LDL-C and tHcy levels in UAP patients (r= 0.355, p= 0.021). The TT genotype frequency was not statistically different between the groups, but T allele carriers exhibited higher tHcy levels in each group. Accordingly, in the AMI group, T allele carriers exhibited the lowest HTLase activities (286.57 vs. 457 and 474.7 U/ml respectively for the UAP and SAP groups). Conclusions: tHcy is an independent predictor of CAD. tHcy levels are dependant of the MTHFR C677T TT genotype and negatively associated with HTLase activity.
77th Congress of the European Atherosclerosis Society, April 26–29, 2008, Istanbul, Turkey
POSTER SESSIONS
Background and aims: Chronic low-grade inflammation is involved in the pathogenesis of many disease conditions in humans and is associated with mortality in elderly people. Upstream transcription factor 1 (USF1) regulates the transcription of more than 40 inflammatory and other cardiovascular related genes. No data, however, exists on the impact of this gene to the mortality in elderly people. Methods: Vitality 90+ population-based study, included all 916 nonagenarians born 1907-1910 who were living in the area of Tampere municipality, Finland, in the year 2000. Altogether 489 nonagenarians (113 males, 376 females) were voluntary participated for the present study. The mortality information of these subjects was collected in year 2004. During the 4 years follow-up the mortality rate was 68.5% (335 out of 489). USF1 genotyping was performed by employing the 5’-nuclease assay and fluorogenic allele-specific TaqMan probes and primers. Results: Here we show that both studied USF1 allelic variants -56C>T (rs2516839) and 5552C>T (rs2774279) had a significant sex by USF1 genotype interaction (p<0.05 for both) in relation to survival. In men the CC genotype of rs2516839 was associated with shorter life expectancy as compared to other genotypes (CT+TT, p=0.02). However, in women CC genotype was significantly associated with lower mortality rate (p=0.046). In men the CC genotype of rs2774279 was associated with shorter life expectancy as compared to other genotypes (CT+TT, p=0.02) while in women CC genotype was significantly associated with lower mortality rate (p=0.046). Conclusion: These data imply that the USF1 gene is a longevity gene in humans.
PO24-352
103
USF1 GENE IS INVOLVED IN THE REGULATION OF HUMAN LONGEVITY
B. Ozsait 1,2,5 , E. Komurcu-Bayrak 1,2,5 , M. Jylha 3 , M. Perola 4 , K. Kristiansson 4 , N. Mononen 1,2 , M. Hurme 1,2 , R. Laaksonen 1,2 , A. Hervonen 3 , N. Erginel-Unaltuna 5 , P. Karhunen 1,2 , T. Lehtimaki 1,2 . 1 University of Tampere Medical School, Tampere, Finland; 2 The Laboratory Centre, Tampere University Hospital, Tampere, Finland; 3 Tampere School of Public Health, Tampere, Finland; 4 Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland; 5 Department of Genetics, Institute for Medical Research, Istanbul University, Istanbul, Turkey
PO24-351
ASSOCIATION OF LIPOPROTEIN LIPASE GENE MARKER WITH LIPID PROFILE IN ESSENTIAL HYPERTENSION
B. Susleyici Duman 1 , C. Ciftci 2 , P. Cagatay 3 . 1 Department of Medical Biology and Genetics, Istanbul Science University Medical Faculty, Istanbul, Turkey; 2 Department of Cardiology, Istanbul Science University Medical Faculty, Florence Nightingale Hospital, Istanbul, Turkey; 3 Department of Biostatistics, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey Background and aims: Lipoprotein lipase (LPL) gene involved in triglycerides metabolism, may be involved in the genetic component of the development of hypertension. In this case-control study, we aimed to determine the association between essential hypertension (EH) and LPL PvuII genotypes as a result of C497→T transition. Additionally, PvuII genotypes were investigated for their association with serum lipids. Methods: The study group was composed of 50 individuals with EH and 51 normotensive controls. PCR-RFLP was used to determine the PvuII variation of the LPL gene. Results: The PvuII C/T, C/C and T/T genotype frequencies were respectively 34%, 24%, 42% in EH; 39.2%, 37.3%, 23.5% in controls. The frequencies of PvuII genotypes did not differ significantly between case and controls. LPL PvuII polymorphism was found to be effective over HDL-cholesterol and total-cholesterol. Total-cholesterol was found to be the higher in mutant (TT) genotype in comparison to CT and CC carriers in both patients and controls. In controls, the highest and lowest HDL-cholesterol levels were respectively found in CC and CT genotypes. Whereas the EH patients with CT had the lowest HDL-cholesterol compared to CC and TT genotypes. With logistic regression analysis LPL gene PvuII genotypes were not found to be associated with EH. Conclusions: Our study failed to reveal an association of LPL PvuII locus with hypertension. However, significant differences were found in HDL- and total-cholesterol levels among PvuII genotypes in EH patients. Larger population-based studies are needed to understand the exact role of LPL gene locus in causing EH.
A COMMON POLYMORPHISM IN THE ATP-BINDING CASSETTE PROTEIN A1 GENE AND HDL-C METABOLISM IN IRAN
S. Halalkhor 1 , S.A. Mesbah-Namin 1 , M.S. Daneshpour 2 , P. Eshragi 2 , M. Hedayati 2 , F. Azizi 2 . 1 Clinical Biochemistry,School of Medical Sciences,Tarbiat Modares University, Tehran, IRAN; 2 Research Institute for Endocrine Sciences, Shaheed Beheshti University of Medical Sciences, Tehran, IRAN Background and aims: Low plasma HDL-C is associated with an increased risk of coronary artery disease (CAD). The ATP-binding cassette transporter-1 (ABCA1) mediates cholesterol efflux and genotypic variation of ABCA1 common polymorphism frequency and its association with HDL-C level in Iranian population. Methods: 700 subjects were selected randomly from the Tehran Lipid Glucose Study center. HDL-C, in ABCA1 and may impact reverse cholesterol transport and influence cardiovascular disease (CVD) risk. The aim of this study was determination LDL-C, TG and FBS levels were determined. Genomic DNA was extracted and the region contains 1051 G/A (R219K) in Exon 7 was amplified by PCR and the polymorphism was reveled by XagI as restriction enzyme in RFLP. Results: The frequency of R219K variant was 63% in the population. HDL-C level showed association with the common polymorphism of ABCA1 gene. Conclusions: The obtained data suggest that the common variation in ABCA1 significantly influences plasma HDL-C levels. PO24-353
AN ASSOCIATION BETWEEN HOMOCYSTEINE, MTHFR C677T GENE POLYMORPHISM, THIOLACTONASE ACTIVITY AND LIPID PARAMETERS IN TUNISIAN CORONARY HEART DISEASE PATIENTS
N. Koubaa 1 , A. Nakbi 1 , K. Ben Hamda 2 , S. Hammami 3 , M. Smaoui 1 , N. Attia 1 , M. Hammami 1 . 1 Laboratory of Biochemistry, UR “Human Nutrition and Metabolic Disorders” Faculty of Medicine, Monastir, Tunisia; 2 Department Cardiology, CHU F.Bourguiba, Monastir, Tunisia; 3 Department of Internal Medicine, CHU F.Bourguiba, Monastir, Tunisia Background and aims: Hyperhomocysteinemia (HHcy) is an important, independent risk factor for atherosclerosis and thrombotic disease. HHcy generates oxidative stress and induces vascular damage. We aimed to evaluate tHcy levels according to CAD severity and their association with MTHFR C677T gene polymorphism, thiolactonase activity (HTLase) and some lipid parameters. Methods: Consecutive 93 patients (60.7±11 years) with angiographically documented CHD were involved and classified into 3 groups according to the severity of CAD manifestations: stable orunstable angina pectoris, (SAP, n= 15; UAP, n= 42) and acute myocardial infarction (AMI, n= 36). Biochemical analysis was performed using validated methods as previously described (Koubaa et al. Clinical Biochemistry 2007). Results: AMI patients showed higher tHcy levels as compared with the SAP ones (17.4 vs. 14 µmol/l, p=0.06) associated with lower HTLase (359.7 vs. 477.9 U/ml, p=0.038). Furthermore, AMI patients exhibited significantly lower HDL-C levels. In the AMI group, tHcy levels were negatively correlated with HTLase activity (r = -0.754, p = 0.00). A positive correlation was found between LDL-C and tHcy levels in UAP patients (r= 0.355, p= 0.021). The TT genotype frequency was not statistically different between the groups, but T allele carriers exhibited higher tHcy levels in each group. Accordingly, in the AMI group, T allele carriers exhibited the lowest HTLase activities (286.57 vs. 457 and 474.7 U/ml respectively for the UAP and SAP groups). Conclusions: tHcy is an independent predictor of CAD. tHcy levels are dependant of the MTHFR C677T TT genotype and negatively associated with HTLase activity.
77th Congress of the European Atherosclerosis Society, April 26–29, 2008, Istanbul, Turkey
POSTER SESSIONS
Background and aims: Chronic low-grade inflammation is involved in the pathogenesis of many disease conditions in humans and is associated with mortality in elderly people. Upstream transcription factor 1 (USF1) regulates the transcription of more than 40 inflammatory and other cardiovascular related genes. No data, however, exists on the impact of this gene to the mortality in elderly people. Methods: Vitality 90+ population-based study, included all 916 nonagenarians born 1907-1910 who were living in the area of Tampere municipality, Finland, in the year 2000. Altogether 489 nonagenarians (113 males, 376 females) were voluntary participated for the present study. The mortality information of these subjects was collected in year 2004. During the 4 years follow-up the mortality rate was 68.5% (335 out of 489). USF1 genotyping was performed by employing the 5’-nuclease assay and fluorogenic allele-specific TaqMan probes and primers. Results: Here we show that both studied USF1 allelic variants -56C>T (rs2516839) and 5552C>T (rs2774279) had a significant sex by USF1 genotype interaction (p<0.05 for both) in relation to survival. In men the CC genotype of rs2516839 was associated with shorter life expectancy as compared to other genotypes (CT+TT, p=0.02). However, in women CC genotype was significantly associated with lower mortality rate (p=0.046). In men the CC genotype of rs2774279 was associated with shorter life expectancy as compared to other genotypes (CT+TT, p=0.02) while in women CC genotype was significantly associated with lower mortality rate (p=0.046). Conclusion: These data imply that the USF1 gene is a longevity gene in humans.
PO24-352
103