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Julie A Johnson - One of the best experts on this subject based on the ideXlab platform.
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genetic variation in the β2 subunit of the voltage gated calcium channel and pharmacogenetic association with adverse cardiovascular outcomes in the international verapamil sr trandolapril study genetic substudy invest genes
Circulation-cardiovascular Genetics, 2010Co-Authors: Yuxin Niu, Taimour Y Langaee, Yan Gong, J I Moss, Rhonda M Cooperdehoff, Carl J Pepine, Heather M Davis, Hazem Elewa, Amber L Beitelshees, Julie A JohnsonAbstract:Background— Single-nucleotide polymorphisms (SNPs) within the regulatory β2 subunit of the voltage-gated calcium channel ( CACNB2 ) may contribute to variable treatment response to antihypertensive drugs and adverse cardiovascular outcomes. Methods and Results— SNPs in CACNB2 from 60 ethnically diverse individuals were identified and characterized. Three common SNPs (rs2357928, rs7069292, and rs61839258) and a genome-wide association study-identified intronic SNP (rs11014166) were genotyped for a clinical association study in 5598 hypertensive patients with coronary artery disease randomized to a β-blocker (BB) or a calcium channel blocker (CCB) treatment strategy in the INternational VErapamil SR-Trandolapril STudy GENEtic Substudy (INVEST-GENES). Reporter gene assays were conducted on the promoter SNP, showing association with clinical outcomes. Twenty-one novel SNPs were identified. A promoter A>G SNP (rs2357928) was found to have significant interaction with treatment strategy for adverse cardiovascular outcomes ( P for interaction, 0.002). In whites, rs2357928 GG patients randomized to CCB were more likely to experience an adverse outcome than those randomized to BB treatment strategy, with adjusted hazard ratio (HR) (CCB versus BB) of 2.35 (95% CI, 1.19 to 4.66; P =0.014). There was no evidence for such treatment difference in AG (HR, 1.16; 95% CI, 0.75 to 1.79; P =0.69) and AA (HR, 0.63; 95% CI, 0.36 to 1.11; P =0.11) patients. This finding was consistent in Hispanics and blacks. CACNB2 rs11014166 showed similar pharmacogenetic effect in Hispanics, but not in whites or blacks. Reporter assay analysis of rs2357928 showed a significant increase in promoter activity for the G allele compared to the A allele. Conclusions— These data suggest that genetic variation within CACNB2 may influence treatment-related outcomes in high-risk patients with hypertension. Clinical Trial Registration— URL: . Unique identifier: [NCT00133692][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00133692&atom=%2Fcirccvg%2F3%2F6%2F548.atom
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abstract 4414 dna variations in voltage gated calcium channel beta 2 subunit CACNB2 gene functional consequences and association with adverse cardiovascular outcomes in the international verapamil sr trandolapril study genetic substudy
Circulation, 2008Co-Authors: Yuxin Niu, Taimour Y Langaee, Yan Gong, J I Moss, Rhonda M Cooperdehoff, Carl J Pepine, Julie A JohnsonAbstract:Background: Genetic variations in the CACNB2 gene, which encodes a regulatory subunit of the L-type calcium channel, have not been thoroughly characterized. We undertook a single nucleotide polymorphism (SNP) discovery effort to characterize SNPs in CACNB2 and to determine if these SNPs were associated with adverse cardiovascular outcomes in patients with hypertension and coronary artery disease (CAD), and if associated, to determine functional underpinnings. Methods: Genomic DNA from 60 ethnically diverse individuals was used for SNP discovery. SNPs from exons, intron/exon junctions, 5′ and 3′UTR of CACNB2 were identified and characterized by direct DNA sequencing. Four common SNPs (rs12764271, rs7069292, rs16917273, and rs2357928) from the 14 SNPs that were predicted to be functional by PolyMApr, were selected for a clinical association study in 1032 hypertensive CAD patients in INVEST-GENES who were randomized to atenolol or verapamil-SR-based treatment. Reporter assays were performed in CHO and HEK293...
Yuxin Niu - One of the best experts on this subject based on the ideXlab platform.
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Genetic Variation in the 2 Subunit of the Voltage-Gated Calcium Channel and Pharmacogenetic Association With Adverse Cardiovascular Outcomes in the INternational VErapamil SR-Trandolapril STudy GENEtic Substudy
2016Co-Authors: Yuxin Niu, Hazem Elewa, Phd* Yan Gong, Y. Langaee, Phd Heather, M. Davis, Phd Amber, L. Beitelshees, Mph James, I. MossAbstract:Background—Single-nucleotide polymorphisms (SNPs) within the regulatory 2 subunit of the voltage-gated calcium channel (CACNB2) may contribute to variable treatment response to antihypertensive drugs and adverse cardiovascular outcomes. Methods and Results—SNPs in CACNB2 from 60 ethnically diverse individuals were identified and characterized. Three common SNPs (rs2357928, rs7069292, and rs61839258) and a genome-wide association study-identified intronic SNP (rs11014166) were genotyped for a clinical association study in 5598 hypertensive patients with coronary artery disease randomized to a -blocker (BB) or a calcium channel blocker (CCB) treatment strategy in the INternational VErapamil SR-Trandolapril STudy GENEtic Substudy (INVEST-GENES). Reporter gene assays were conducted on the promoter SNP, showing association with clinical outcomes. Twenty-one novel SNPs were identified. A promoter AG SNP (rs2357928) was found to have significant interaction with treatment strategy for adverse cardiovascular outcomes (P for interaction, 0.002). In whites, rs2357928 GG patients randomized to CCB were more likely to experience an adverse outcome than those randomized to BB treatment strategy, with adjusted hazard ratio (HR) (CCB versus BB) of 2.35 (95% CI, 1.19 to 4.66; P0.014). There was no evidence for such treatment difference in AG (HR, 1.16; 95 % CI, 0.75 to 1.79; P0.69) and AA (HR, 0.63; 95 % CI, 0.36 to 1.11; P0.11) patients. This finding was consistent in Hispanics and blacks. CACNB2 rs11014166 showed similar pharmacogenetic effect in Hispanics, but not in whites or blacks. Reporter assa
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genetic variation in the β2 subunit of the voltage gated calcium channel and pharmacogenetic association with adverse cardiovascular outcomes in the international verapamil sr trandolapril study genetic substudy invest genes
Circulation-cardiovascular Genetics, 2010Co-Authors: Yuxin Niu, Taimour Y Langaee, Yan Gong, J I Moss, Rhonda M Cooperdehoff, Carl J Pepine, Heather M Davis, Hazem Elewa, Amber L Beitelshees, Julie A JohnsonAbstract:Background— Single-nucleotide polymorphisms (SNPs) within the regulatory β2 subunit of the voltage-gated calcium channel ( CACNB2 ) may contribute to variable treatment response to antihypertensive drugs and adverse cardiovascular outcomes. Methods and Results— SNPs in CACNB2 from 60 ethnically diverse individuals were identified and characterized. Three common SNPs (rs2357928, rs7069292, and rs61839258) and a genome-wide association study-identified intronic SNP (rs11014166) were genotyped for a clinical association study in 5598 hypertensive patients with coronary artery disease randomized to a β-blocker (BB) or a calcium channel blocker (CCB) treatment strategy in the INternational VErapamil SR-Trandolapril STudy GENEtic Substudy (INVEST-GENES). Reporter gene assays were conducted on the promoter SNP, showing association with clinical outcomes. Twenty-one novel SNPs were identified. A promoter A>G SNP (rs2357928) was found to have significant interaction with treatment strategy for adverse cardiovascular outcomes ( P for interaction, 0.002). In whites, rs2357928 GG patients randomized to CCB were more likely to experience an adverse outcome than those randomized to BB treatment strategy, with adjusted hazard ratio (HR) (CCB versus BB) of 2.35 (95% CI, 1.19 to 4.66; P =0.014). There was no evidence for such treatment difference in AG (HR, 1.16; 95% CI, 0.75 to 1.79; P =0.69) and AA (HR, 0.63; 95% CI, 0.36 to 1.11; P =0.11) patients. This finding was consistent in Hispanics and blacks. CACNB2 rs11014166 showed similar pharmacogenetic effect in Hispanics, but not in whites or blacks. Reporter assay analysis of rs2357928 showed a significant increase in promoter activity for the G allele compared to the A allele. Conclusions— These data suggest that genetic variation within CACNB2 may influence treatment-related outcomes in high-risk patients with hypertension. Clinical Trial Registration— URL: . Unique identifier: [NCT00133692][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00133692&atom=%2Fcirccvg%2F3%2F6%2F548.atom
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abstract 4414 dna variations in voltage gated calcium channel beta 2 subunit CACNB2 gene functional consequences and association with adverse cardiovascular outcomes in the international verapamil sr trandolapril study genetic substudy
Circulation, 2008Co-Authors: Yuxin Niu, Taimour Y Langaee, Yan Gong, J I Moss, Rhonda M Cooperdehoff, Carl J Pepine, Julie A JohnsonAbstract:Background: Genetic variations in the CACNB2 gene, which encodes a regulatory subunit of the L-type calcium channel, have not been thoroughly characterized. We undertook a single nucleotide polymorphism (SNP) discovery effort to characterize SNPs in CACNB2 and to determine if these SNPs were associated with adverse cardiovascular outcomes in patients with hypertension and coronary artery disease (CAD), and if associated, to determine functional underpinnings. Methods: Genomic DNA from 60 ethnically diverse individuals was used for SNP discovery. SNPs from exons, intron/exon junctions, 5′ and 3′UTR of CACNB2 were identified and characterized by direct DNA sequencing. Four common SNPs (rs12764271, rs7069292, rs16917273, and rs2357928) from the 14 SNPs that were predicted to be functional by PolyMApr, were selected for a clinical association study in 1032 hypertensive CAD patients in INVEST-GENES who were randomized to atenolol or verapamil-SR-based treatment. Reporter assays were performed in CHO and HEK293...
Yan Gong - One of the best experts on this subject based on the ideXlab platform.
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genetic variation in the β2 subunit of the voltage gated calcium channel and pharmacogenetic association with adverse cardiovascular outcomes in the international verapamil sr trandolapril study genetic substudy invest genes
Circulation-cardiovascular Genetics, 2010Co-Authors: Yuxin Niu, Taimour Y Langaee, Yan Gong, J I Moss, Rhonda M Cooperdehoff, Carl J Pepine, Heather M Davis, Hazem Elewa, Amber L Beitelshees, Julie A JohnsonAbstract:Background— Single-nucleotide polymorphisms (SNPs) within the regulatory β2 subunit of the voltage-gated calcium channel ( CACNB2 ) may contribute to variable treatment response to antihypertensive drugs and adverse cardiovascular outcomes. Methods and Results— SNPs in CACNB2 from 60 ethnically diverse individuals were identified and characterized. Three common SNPs (rs2357928, rs7069292, and rs61839258) and a genome-wide association study-identified intronic SNP (rs11014166) were genotyped for a clinical association study in 5598 hypertensive patients with coronary artery disease randomized to a β-blocker (BB) or a calcium channel blocker (CCB) treatment strategy in the INternational VErapamil SR-Trandolapril STudy GENEtic Substudy (INVEST-GENES). Reporter gene assays were conducted on the promoter SNP, showing association with clinical outcomes. Twenty-one novel SNPs were identified. A promoter A>G SNP (rs2357928) was found to have significant interaction with treatment strategy for adverse cardiovascular outcomes ( P for interaction, 0.002). In whites, rs2357928 GG patients randomized to CCB were more likely to experience an adverse outcome than those randomized to BB treatment strategy, with adjusted hazard ratio (HR) (CCB versus BB) of 2.35 (95% CI, 1.19 to 4.66; P =0.014). There was no evidence for such treatment difference in AG (HR, 1.16; 95% CI, 0.75 to 1.79; P =0.69) and AA (HR, 0.63; 95% CI, 0.36 to 1.11; P =0.11) patients. This finding was consistent in Hispanics and blacks. CACNB2 rs11014166 showed similar pharmacogenetic effect in Hispanics, but not in whites or blacks. Reporter assay analysis of rs2357928 showed a significant increase in promoter activity for the G allele compared to the A allele. Conclusions— These data suggest that genetic variation within CACNB2 may influence treatment-related outcomes in high-risk patients with hypertension. Clinical Trial Registration— URL: . Unique identifier: [NCT00133692][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00133692&atom=%2Fcirccvg%2F3%2F6%2F548.atom
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abstract 4414 dna variations in voltage gated calcium channel beta 2 subunit CACNB2 gene functional consequences and association with adverse cardiovascular outcomes in the international verapamil sr trandolapril study genetic substudy
Circulation, 2008Co-Authors: Yuxin Niu, Taimour Y Langaee, Yan Gong, J I Moss, Rhonda M Cooperdehoff, Carl J Pepine, Julie A JohnsonAbstract:Background: Genetic variations in the CACNB2 gene, which encodes a regulatory subunit of the L-type calcium channel, have not been thoroughly characterized. We undertook a single nucleotide polymorphism (SNP) discovery effort to characterize SNPs in CACNB2 and to determine if these SNPs were associated with adverse cardiovascular outcomes in patients with hypertension and coronary artery disease (CAD), and if associated, to determine functional underpinnings. Methods: Genomic DNA from 60 ethnically diverse individuals was used for SNP discovery. SNPs from exons, intron/exon junctions, 5′ and 3′UTR of CACNB2 were identified and characterized by direct DNA sequencing. Four common SNPs (rs12764271, rs7069292, rs16917273, and rs2357928) from the 14 SNPs that were predicted to be functional by PolyMApr, were selected for a clinical association study in 1032 hypertensive CAD patients in INVEST-GENES who were randomized to atenolol or verapamil-SR-based treatment. Reporter assays were performed in CHO and HEK293...
Carl J Pepine - One of the best experts on this subject based on the ideXlab platform.
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genetic variation in the β2 subunit of the voltage gated calcium channel and pharmacogenetic association with adverse cardiovascular outcomes in the international verapamil sr trandolapril study genetic substudy invest genes
Circulation-cardiovascular Genetics, 2010Co-Authors: Yuxin Niu, Taimour Y Langaee, Yan Gong, J I Moss, Rhonda M Cooperdehoff, Carl J Pepine, Heather M Davis, Hazem Elewa, Amber L Beitelshees, Julie A JohnsonAbstract:Background— Single-nucleotide polymorphisms (SNPs) within the regulatory β2 subunit of the voltage-gated calcium channel ( CACNB2 ) may contribute to variable treatment response to antihypertensive drugs and adverse cardiovascular outcomes. Methods and Results— SNPs in CACNB2 from 60 ethnically diverse individuals were identified and characterized. Three common SNPs (rs2357928, rs7069292, and rs61839258) and a genome-wide association study-identified intronic SNP (rs11014166) were genotyped for a clinical association study in 5598 hypertensive patients with coronary artery disease randomized to a β-blocker (BB) or a calcium channel blocker (CCB) treatment strategy in the INternational VErapamil SR-Trandolapril STudy GENEtic Substudy (INVEST-GENES). Reporter gene assays were conducted on the promoter SNP, showing association with clinical outcomes. Twenty-one novel SNPs were identified. A promoter A>G SNP (rs2357928) was found to have significant interaction with treatment strategy for adverse cardiovascular outcomes ( P for interaction, 0.002). In whites, rs2357928 GG patients randomized to CCB were more likely to experience an adverse outcome than those randomized to BB treatment strategy, with adjusted hazard ratio (HR) (CCB versus BB) of 2.35 (95% CI, 1.19 to 4.66; P =0.014). There was no evidence for such treatment difference in AG (HR, 1.16; 95% CI, 0.75 to 1.79; P =0.69) and AA (HR, 0.63; 95% CI, 0.36 to 1.11; P =0.11) patients. This finding was consistent in Hispanics and blacks. CACNB2 rs11014166 showed similar pharmacogenetic effect in Hispanics, but not in whites or blacks. Reporter assay analysis of rs2357928 showed a significant increase in promoter activity for the G allele compared to the A allele. Conclusions— These data suggest that genetic variation within CACNB2 may influence treatment-related outcomes in high-risk patients with hypertension. Clinical Trial Registration— URL: . Unique identifier: [NCT00133692][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00133692&atom=%2Fcirccvg%2F3%2F6%2F548.atom
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abstract 4414 dna variations in voltage gated calcium channel beta 2 subunit CACNB2 gene functional consequences and association with adverse cardiovascular outcomes in the international verapamil sr trandolapril study genetic substudy
Circulation, 2008Co-Authors: Yuxin Niu, Taimour Y Langaee, Yan Gong, J I Moss, Rhonda M Cooperdehoff, Carl J Pepine, Julie A JohnsonAbstract:Background: Genetic variations in the CACNB2 gene, which encodes a regulatory subunit of the L-type calcium channel, have not been thoroughly characterized. We undertook a single nucleotide polymorphism (SNP) discovery effort to characterize SNPs in CACNB2 and to determine if these SNPs were associated with adverse cardiovascular outcomes in patients with hypertension and coronary artery disease (CAD), and if associated, to determine functional underpinnings. Methods: Genomic DNA from 60 ethnically diverse individuals was used for SNP discovery. SNPs from exons, intron/exon junctions, 5′ and 3′UTR of CACNB2 were identified and characterized by direct DNA sequencing. Four common SNPs (rs12764271, rs7069292, rs16917273, and rs2357928) from the 14 SNPs that were predicted to be functional by PolyMApr, were selected for a clinical association study in 1032 hypertensive CAD patients in INVEST-GENES who were randomized to atenolol or verapamil-SR-based treatment. Reporter assays were performed in CHO and HEK293...
Rhonda M Cooperdehoff - One of the best experts on this subject based on the ideXlab platform.
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genetic variation in the β2 subunit of the voltage gated calcium channel and pharmacogenetic association with adverse cardiovascular outcomes in the international verapamil sr trandolapril study genetic substudy invest genes
Circulation-cardiovascular Genetics, 2010Co-Authors: Yuxin Niu, Taimour Y Langaee, Yan Gong, J I Moss, Rhonda M Cooperdehoff, Carl J Pepine, Heather M Davis, Hazem Elewa, Amber L Beitelshees, Julie A JohnsonAbstract:Background— Single-nucleotide polymorphisms (SNPs) within the regulatory β2 subunit of the voltage-gated calcium channel ( CACNB2 ) may contribute to variable treatment response to antihypertensive drugs and adverse cardiovascular outcomes. Methods and Results— SNPs in CACNB2 from 60 ethnically diverse individuals were identified and characterized. Three common SNPs (rs2357928, rs7069292, and rs61839258) and a genome-wide association study-identified intronic SNP (rs11014166) were genotyped for a clinical association study in 5598 hypertensive patients with coronary artery disease randomized to a β-blocker (BB) or a calcium channel blocker (CCB) treatment strategy in the INternational VErapamil SR-Trandolapril STudy GENEtic Substudy (INVEST-GENES). Reporter gene assays were conducted on the promoter SNP, showing association with clinical outcomes. Twenty-one novel SNPs were identified. A promoter A>G SNP (rs2357928) was found to have significant interaction with treatment strategy for adverse cardiovascular outcomes ( P for interaction, 0.002). In whites, rs2357928 GG patients randomized to CCB were more likely to experience an adverse outcome than those randomized to BB treatment strategy, with adjusted hazard ratio (HR) (CCB versus BB) of 2.35 (95% CI, 1.19 to 4.66; P =0.014). There was no evidence for such treatment difference in AG (HR, 1.16; 95% CI, 0.75 to 1.79; P =0.69) and AA (HR, 0.63; 95% CI, 0.36 to 1.11; P =0.11) patients. This finding was consistent in Hispanics and blacks. CACNB2 rs11014166 showed similar pharmacogenetic effect in Hispanics, but not in whites or blacks. Reporter assay analysis of rs2357928 showed a significant increase in promoter activity for the G allele compared to the A allele. Conclusions— These data suggest that genetic variation within CACNB2 may influence treatment-related outcomes in high-risk patients with hypertension. Clinical Trial Registration— URL: . Unique identifier: [NCT00133692][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00133692&atom=%2Fcirccvg%2F3%2F6%2F548.atom
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abstract 4414 dna variations in voltage gated calcium channel beta 2 subunit CACNB2 gene functional consequences and association with adverse cardiovascular outcomes in the international verapamil sr trandolapril study genetic substudy
Circulation, 2008Co-Authors: Yuxin Niu, Taimour Y Langaee, Yan Gong, J I Moss, Rhonda M Cooperdehoff, Carl J Pepine, Julie A JohnsonAbstract:Background: Genetic variations in the CACNB2 gene, which encodes a regulatory subunit of the L-type calcium channel, have not been thoroughly characterized. We undertook a single nucleotide polymorphism (SNP) discovery effort to characterize SNPs in CACNB2 and to determine if these SNPs were associated with adverse cardiovascular outcomes in patients with hypertension and coronary artery disease (CAD), and if associated, to determine functional underpinnings. Methods: Genomic DNA from 60 ethnically diverse individuals was used for SNP discovery. SNPs from exons, intron/exon junctions, 5′ and 3′UTR of CACNB2 were identified and characterized by direct DNA sequencing. Four common SNPs (rs12764271, rs7069292, rs16917273, and rs2357928) from the 14 SNPs that were predicted to be functional by PolyMApr, were selected for a clinical association study in 1032 hypertensive CAD patients in INVEST-GENES who were randomized to atenolol or verapamil-SR-based treatment. Reporter assays were performed in CHO and HEK293...
