- Email: [email protected]
The mutation r3500q of apolipoprotein b in caucasian population of west siberia and in patients with highest total cholesterol level
e100
Abstracts / Atherosclerosis 235 (2014) e84–e191
proteins and DNA repair. However, HMUFA, LFHCC and LFHCC n-3 diets down-regulated pro-inflammatory- and oxidative stress-related proteins and DNA repairing proteins. Conclusion: The long term consumption of HSFA, compared to HMUFA, LFHCC and LFHCC n-3, may increase the atherosclerosis risk factors associated with the metabolic syndrome such as inflammation and oxidative stress, and could lead to DNA damage as consequence of high oxidative stress. 05 - Genomics and proteomics of lipid metabolism EAS-0394. TARGETED NEXT GENERATION SEQUENCING FOR GENETIC DIAGNOSIS OF FAMILIAL HYPERCHOLESTEROLEMIA C. Maglioa, R.M. Mancinab, B.M. Mottac, C. Pirazzia, O. Wiklunda, S. Romeoa a
Department of Molecular and Clinical Medicine, Institute of Medicine University of Gothenburg, Gothenburg, Sweden; b Department of Medical and Surgical Sciences, University Magna Graecia, Catanzaro, Italy; c Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy Objectives: Familial Hypercholesterolemia (FH) is a genetic disorder of lowdensity lipoprotein cholesterol (LDL-C) metabolism characterized by high serum levels of LDL-cholesterol. FH diagnosis is based on clinical scores or can be achieved by genetic diagnosis. Recently targeted next generation sequencing has been validated to screen FH related genes but it showed a low diagnosis success rate in individuals with hypercholesterolemia. The aim of this study was to combine clinical criteria and next generation sequencing to achieve FH diagnosis in individuals at high risk. Methods: The project was approved by the regional Ethics Committee of Gothenburg. The study includes 77 apparently unrelated adults with Dutch Lipid Clinic score 3. DNA was extracted by blood in all subjects and sequenced by SEQPRO LIPO RS (Progenika Biopharma, Spain). SEQPRO LIPO RS is a next generation sequencing (pyrosequencing) kit designed to detect mutations in the LDLR, APOB, PCSK9 and LDRAP1 genes. Copy number variations in the LDLR gene were also examined. Results: Overall a total of 26 different FH-related mutations were detected in 50 out of 77 subjects (65%). Among these, 23 mutations (in 90% of the subjects) were in the LDLR gene, 2 (in 8% of the subjects) in the APOB gene and 1 (in 4% of the subjects) in the PCSK9 gene. We detected 4 unknown pathogenicity mutations in the LDLR gene. Among these mutations, 3 (Gly505Asp, Ile585Thr and Gln660Arg) have been previously reported in subjects with FH. One splicing mutation has never been reported before and segregates with high LDL-C levels in the proband's family suggesting that it may be causative of FH. Conclusion: We have successfully diagnosed FH individuals with a high success rate by using a combination of clinical criteria and targeted pyrosequencing. Furthermore we identified a new mutation in the LDL-R gene affecting a splicing site. 05 - Genomics and proteomics of lipid metabolism EAS-0423. THE MUTATION R3500Q OF APOLIPOPROTEIN B IN CAUCASIAN POPULATION OF WEST SIBERIA AND IN PATIENTS WITH HIGHEST TOTAL CHOLESTEROL LEVEL M. Voevodaa, E. Shakhtshneidera, P. Orlova, D. Ivanoshchuka, M. Ivanovab, Y. Nikitinc, S. Malyutinac a Laboratory of Genetics of Internal Medicine, Federal State Budgetary Institution of Internal and Preventive Medicine SB RAMS, Novosibirsk, Russia; b Laboratory of Biochemistry, Federal State Budgetary Institution of Internal and Preventive Medicine SB RAMS, Novosibirsk, Russia; c Laboratory of Internal Medicine, Federal State Budgetary Institution of Internal and Preventive Medicine SB RAMS, Novosibirsk, Russia
Objectives: The study was aimed at the analysis of the rare mutation R3500Q of apolipoprotein B (APOB) in Caucasian (Russians) population of West Siberia and in patients with high total cholesterol level.
Methods: The Caucasian patients included in the analyses were selected based on total cholesterol (TC) level from population sample surveyed in frame of HAPIEE project (9600 participants, aged 45-69, men/women – 50/ 50%). Totally 267 patients with highest total cholesterol level (TC>300mg/ dl; mean TC level 353.257.0mg/dl) and 92 randomly selected patients (mean TC level - 237.350.0mg/dl) were included in the analyses. The plasma lipids levels were determined by standard enzymatic assays. The mutation R3500Q of APOB (rs5742904) was analyzed by RT-PCR. Results: The mutation R3500Q of APOB was absent in HAPIEE population group. The frequency in Russian population was close to previously reported data for other Caucasian population (<0.5%). The frequency of 3500Q allele was 0.9% in the group with highest TC level. Five heterozygous genotypes were detected in the group with highest TC level (men/women – 40/60%). We have found the association of APOB R3500Q with total cholesterol level and LDL-C level in the group with highest TC level (p¼0.041 and p¼0.000, respectively). Conclusion: The frequency of APOB R3500Q is low in Caucasian (Russians) population of West Siberia. The mutation R3500Q of APOB has been associated with high TC level and LDL-C level the group with highest TC level in Caucasian of West Siberia. The reported study was partially supported by RFBR, research project N1404-01594a. 05 - Genomics and proteomics of lipid metabolism EAS-0464. RARE POLYMORPHISM GLN3405GLU OF APOLIPOPROTEIN B IN CAUCASIAN POPULATION OF WEST SIBERIA AND ITS ASSOCIATION WITH PLASMA LIPIDS LEVELS M. Voevodaa, E. Shakhtshneidera, M. Ivanovab, Y. Nikitinc, S. Malyutinac a
Laboratory of Genetics of Internal Medicine, Federal State Budgetary Institution of Internal and Preventive Medicine Siberian, Novosibirsk, Russia; b Laboratory of Biochemistry, Federal State Budgetary Institution of Internal and Preventive Medicine Siberian, Novosibirsk, Russia; c Laboratory of Internal Medicine, Federal State Budgetary Institution of Internal and Preventive Medicine Siberian, Novosibirsk, Russia Objectives: The study was aimed at the analysis of the rare polymorphism Gln3405Glu of apolipoprotein B (APOB) in Caucasian population of West Siberia and in patients with low and high total cholesterol level. Polymorphism Gln3405Glu is located in the putative receptor-binding domain of APOB. Few papers report the low population frequency of this variant in Caucasian population (<1%) and provide controversial data on its phenotypic expression. Methods: The Caucasian patients included in the analyses were selected based on total cholesterol (TC) level from population sample surveyed in frame of HAPIEE project (w9000 participants, aged 45-69, men/women – 50/50%). Totally 98 patients with highest total cholesterol level (TC>300mg/dl), 94 patients with low total cholesterol level (TC<200mg/ dl) and 102 randomly selected patients (mean TC level - 233.647.7mg/dl) were included in the analyses. The plasma lipids levels were determined by standard enzymatic assays. Gln3405Glu polymorphism of APOB (Gln3405Glu) gene was analyzed by original method. Results: The frequency of polymorphism Gln3405Glu of APOB gene in Russian population was close to previously reported data for other Caucasian population (w0.5%). The frequency of 3405Glu allele was 0.49%, 0.53% and 4.1% in HAPIEE population, low and highest TC level groups, respectively (p<0.05). Two homozygous genotypes and four heterozygous genotypes were detected in group with highest TC level. Conclusion: The frequency of 3405Glu allele is low in majority of Caucasian populations. This study demonstrated the association of this allele with elevated total cholesterol level in Caucasians population of West Siberia. The reported study was partially supported by RFBR, research project N1404-01594a. 05 - Genomics and proteomics of lipid metabolism EAS-0456. THE HINDIII POLYMORPHISM OF LIPOPROTEIN LIPASE GENE AND LIPID PROFILE IN CAUCASIAN POPULATION OF WEST SIBERIA
Abstracts / Atherosclerosis 235 (2014) e84–e191
proteins and DNA repair. However, HMUFA, LFHCC and LFHCC n-3 diets down-regulated pro-inflammatory- and oxidative stress-related proteins and DNA repairing proteins. Conclusion: The long term consumption of HSFA, compared to HMUFA, LFHCC and LFHCC n-3, may increase the atherosclerosis risk factors associated with the metabolic syndrome such as inflammation and oxidative stress, and could lead to DNA damage as consequence of high oxidative stress. 05 - Genomics and proteomics of lipid metabolism EAS-0394. TARGETED NEXT GENERATION SEQUENCING FOR GENETIC DIAGNOSIS OF FAMILIAL HYPERCHOLESTEROLEMIA C. Maglioa, R.M. Mancinab, B.M. Mottac, C. Pirazzia, O. Wiklunda, S. Romeoa a
Department of Molecular and Clinical Medicine, Institute of Medicine University of Gothenburg, Gothenburg, Sweden; b Department of Medical and Surgical Sciences, University Magna Graecia, Catanzaro, Italy; c Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy Objectives: Familial Hypercholesterolemia (FH) is a genetic disorder of lowdensity lipoprotein cholesterol (LDL-C) metabolism characterized by high serum levels of LDL-cholesterol. FH diagnosis is based on clinical scores or can be achieved by genetic diagnosis. Recently targeted next generation sequencing has been validated to screen FH related genes but it showed a low diagnosis success rate in individuals with hypercholesterolemia. The aim of this study was to combine clinical criteria and next generation sequencing to achieve FH diagnosis in individuals at high risk. Methods: The project was approved by the regional Ethics Committee of Gothenburg. The study includes 77 apparently unrelated adults with Dutch Lipid Clinic score 3. DNA was extracted by blood in all subjects and sequenced by SEQPRO LIPO RS (Progenika Biopharma, Spain). SEQPRO LIPO RS is a next generation sequencing (pyrosequencing) kit designed to detect mutations in the LDLR, APOB, PCSK9 and LDRAP1 genes. Copy number variations in the LDLR gene were also examined. Results: Overall a total of 26 different FH-related mutations were detected in 50 out of 77 subjects (65%). Among these, 23 mutations (in 90% of the subjects) were in the LDLR gene, 2 (in 8% of the subjects) in the APOB gene and 1 (in 4% of the subjects) in the PCSK9 gene. We detected 4 unknown pathogenicity mutations in the LDLR gene. Among these mutations, 3 (Gly505Asp, Ile585Thr and Gln660Arg) have been previously reported in subjects with FH. One splicing mutation has never been reported before and segregates with high LDL-C levels in the proband's family suggesting that it may be causative of FH. Conclusion: We have successfully diagnosed FH individuals with a high success rate by using a combination of clinical criteria and targeted pyrosequencing. Furthermore we identified a new mutation in the LDL-R gene affecting a splicing site. 05 - Genomics and proteomics of lipid metabolism EAS-0423. THE MUTATION R3500Q OF APOLIPOPROTEIN B IN CAUCASIAN POPULATION OF WEST SIBERIA AND IN PATIENTS WITH HIGHEST TOTAL CHOLESTEROL LEVEL M. Voevodaa, E. Shakhtshneidera, P. Orlova, D. Ivanoshchuka, M. Ivanovab, Y. Nikitinc, S. Malyutinac a Laboratory of Genetics of Internal Medicine, Federal State Budgetary Institution of Internal and Preventive Medicine SB RAMS, Novosibirsk, Russia; b Laboratory of Biochemistry, Federal State Budgetary Institution of Internal and Preventive Medicine SB RAMS, Novosibirsk, Russia; c Laboratory of Internal Medicine, Federal State Budgetary Institution of Internal and Preventive Medicine SB RAMS, Novosibirsk, Russia
Objectives: The study was aimed at the analysis of the rare mutation R3500Q of apolipoprotein B (APOB) in Caucasian (Russians) population of West Siberia and in patients with high total cholesterol level.
Methods: The Caucasian patients included in the analyses were selected based on total cholesterol (TC) level from population sample surveyed in frame of HAPIEE project (9600 participants, aged 45-69, men/women – 50/ 50%). Totally 267 patients with highest total cholesterol level (TC>300mg/ dl; mean TC level 353.257.0mg/dl) and 92 randomly selected patients (mean TC level - 237.350.0mg/dl) were included in the analyses. The plasma lipids levels were determined by standard enzymatic assays. The mutation R3500Q of APOB (rs5742904) was analyzed by RT-PCR. Results: The mutation R3500Q of APOB was absent in HAPIEE population group. The frequency in Russian population was close to previously reported data for other Caucasian population (<0.5%). The frequency of 3500Q allele was 0.9% in the group with highest TC level. Five heterozygous genotypes were detected in the group with highest TC level (men/women – 40/60%). We have found the association of APOB R3500Q with total cholesterol level and LDL-C level in the group with highest TC level (p¼0.041 and p¼0.000, respectively). Conclusion: The frequency of APOB R3500Q is low in Caucasian (Russians) population of West Siberia. The mutation R3500Q of APOB has been associated with high TC level and LDL-C level the group with highest TC level in Caucasian of West Siberia. The reported study was partially supported by RFBR, research project N1404-01594a. 05 - Genomics and proteomics of lipid metabolism EAS-0464. RARE POLYMORPHISM GLN3405GLU OF APOLIPOPROTEIN B IN CAUCASIAN POPULATION OF WEST SIBERIA AND ITS ASSOCIATION WITH PLASMA LIPIDS LEVELS M. Voevodaa, E. Shakhtshneidera, M. Ivanovab, Y. Nikitinc, S. Malyutinac a
Laboratory of Genetics of Internal Medicine, Federal State Budgetary Institution of Internal and Preventive Medicine Siberian, Novosibirsk, Russia; b Laboratory of Biochemistry, Federal State Budgetary Institution of Internal and Preventive Medicine Siberian, Novosibirsk, Russia; c Laboratory of Internal Medicine, Federal State Budgetary Institution of Internal and Preventive Medicine Siberian, Novosibirsk, Russia Objectives: The study was aimed at the analysis of the rare polymorphism Gln3405Glu of apolipoprotein B (APOB) in Caucasian population of West Siberia and in patients with low and high total cholesterol level. Polymorphism Gln3405Glu is located in the putative receptor-binding domain of APOB. Few papers report the low population frequency of this variant in Caucasian population (<1%) and provide controversial data on its phenotypic expression. Methods: The Caucasian patients included in the analyses were selected based on total cholesterol (TC) level from population sample surveyed in frame of HAPIEE project (w9000 participants, aged 45-69, men/women – 50/50%). Totally 98 patients with highest total cholesterol level (TC>300mg/dl), 94 patients with low total cholesterol level (TC<200mg/ dl) and 102 randomly selected patients (mean TC level - 233.647.7mg/dl) were included in the analyses. The plasma lipids levels were determined by standard enzymatic assays. Gln3405Glu polymorphism of APOB (Gln3405Glu) gene was analyzed by original method. Results: The frequency of polymorphism Gln3405Glu of APOB gene in Russian population was close to previously reported data for other Caucasian population (w0.5%). The frequency of 3405Glu allele was 0.49%, 0.53% and 4.1% in HAPIEE population, low and highest TC level groups, respectively (p<0.05). Two homozygous genotypes and four heterozygous genotypes were detected in group with highest TC level. Conclusion: The frequency of 3405Glu allele is low in majority of Caucasian populations. This study demonstrated the association of this allele with elevated total cholesterol level in Caucasians population of West Siberia. The reported study was partially supported by RFBR, research project N1404-01594a. 05 - Genomics and proteomics of lipid metabolism EAS-0456. THE HINDIII POLYMORPHISM OF LIPOPROTEIN LIPASE GENE AND LIPID PROFILE IN CAUCASIAN POPULATION OF WEST SIBERIA