Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: the Framingham Study
Genetic variation at the apolipoprotein A5 gene (APOA5) is associated with increased triglyceride concentrations, a risk factor for atherosclerosis. Carotid intimal medial thickness (IMT) is a surrogate measure of atherosclerosis burden. We sought to determine the association of common APOA5 genetic...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2006-05-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520332478 |
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| author | Roberto Elosua Jose M. Ordovas L. Adrienne Cupples Chao-Qiang Lai Serkalem Demissie Caroline S. Fox Joseph F. Polak Philip A. Wolf Ralph B. D'Agostino, Sr. Christopher J. O'Donnell |
| author_facet | Roberto Elosua Jose M. Ordovas L. Adrienne Cupples Chao-Qiang Lai Serkalem Demissie Caroline S. Fox Joseph F. Polak Philip A. Wolf Ralph B. D'Agostino, Sr. Christopher J. O'Donnell |
| author_sort | Roberto Elosua |
| collection | DOAJ |
| description | Genetic variation at the apolipoprotein A5 gene (APOA5) is associated with increased triglyceride concentrations, a risk factor for atherosclerosis. Carotid intimal medial thickness (IMT) is a surrogate measure of atherosclerosis burden. We sought to determine the association of common APOA5 genetic variants with carotid IMT and stenosis. A total of 2,273 Framingham Offspring Study participants underwent carotid ultrasound and had data on at least one of the five APOA5 variants (−1131T>C, −3A>G, 56C>G, IVS3+476G >A, and 1259T>C). Although none of the individual variants was significantly associated with carotid measures, the haplotype defined by the presence of the rare allele of the 56C>G variant was associated with a higher common carotid artery (CCA) IMT compared with the wild-type haplotype (0.75 vs. 0.73 mm; P < 0.05). The rare allele of each of the −1131T >C, −3A>G, IVS3+476G>A, and 1259T>C variants and the haplotype defined by the presence of the rare alleles in these four variants were each significantly associated with CCA IMT in obese participants. These associations remained significant even after adjustment for triglycerides. APOA5 variants were associated with CCA IMT, particularly in obese participants. The mechanism of these associations and the effect modification by obesity are independent of fasting triglyceride levels. |
| first_indexed | 2024-12-17T07:24:36Z |
| format | Article |
| id | doaj.art-58149b458b7545428f0771051665d54e |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T07:24:36Z |
| publishDate | 2006-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-58149b458b7545428f0771051665d54e2022-12-21T21:58:40ZengElsevierJournal of Lipid Research0022-22752006-05-01475990996Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: the Framingham StudyRoberto Elosua0Jose M. Ordovas1L. Adrienne Cupples2Chao-Qiang Lai3Serkalem Demissie4Caroline S. Fox5Joseph F. Polak6Philip A. Wolf7Ralph B. D'Agostino, Sr.8Christopher J. O'Donnell9U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA; Department of Biostatistics, Boston University School of Public Health, Boston, MA; Institut Municipal d’Investigacioé Meèdica, Barcelona, SpainU.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MADepartment of Biostatistics, Boston University School of Public Health, Boston, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MAU.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MADepartment of Biostatistics, Boston University School of Public Health, Boston, MANational Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MDDepartment of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MANational Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA; Departments of Neurology and Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, MANational Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MANational Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MAGenetic variation at the apolipoprotein A5 gene (APOA5) is associated with increased triglyceride concentrations, a risk factor for atherosclerosis. Carotid intimal medial thickness (IMT) is a surrogate measure of atherosclerosis burden. We sought to determine the association of common APOA5 genetic variants with carotid IMT and stenosis. A total of 2,273 Framingham Offspring Study participants underwent carotid ultrasound and had data on at least one of the five APOA5 variants (−1131T>C, −3A>G, 56C>G, IVS3+476G >A, and 1259T>C). Although none of the individual variants was significantly associated with carotid measures, the haplotype defined by the presence of the rare allele of the 56C>G variant was associated with a higher common carotid artery (CCA) IMT compared with the wild-type haplotype (0.75 vs. 0.73 mm; P < 0.05). The rare allele of each of the −1131T >C, −3A>G, IVS3+476G>A, and 1259T>C variants and the haplotype defined by the presence of the rare alleles in these four variants were each significantly associated with CCA IMT in obese participants. These associations remained significant even after adjustment for triglycerides. APOA5 variants were associated with CCA IMT, particularly in obese participants. The mechanism of these associations and the effect modification by obesity are independent of fasting triglyceride levels.http://www.sciencedirect.com/science/article/pii/S0022227520332478apolipoproteinscarotid arteriesepidemiologygeneticsapolipoprotein A5 gene |
| spellingShingle | Roberto Elosua Jose M. Ordovas L. Adrienne Cupples Chao-Qiang Lai Serkalem Demissie Caroline S. Fox Joseph F. Polak Philip A. Wolf Ralph B. D'Agostino, Sr. Christopher J. O'Donnell Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: the Framingham Study Journal of Lipid Research apolipoproteins carotid arteries epidemiology genetics apolipoprotein A5 gene |
| title | Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: the Framingham Study |
| title_full | Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: the Framingham Study |
| title_fullStr | Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: the Framingham Study |
| title_full_unstemmed | Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: the Framingham Study |
| title_short | Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: the Framingham Study |
| title_sort | variants at the apoa5 locus association with carotid atherosclerosis and modification by obesity the framingham study |
| topic | apolipoproteins carotid arteries epidemiology genetics apolipoprotein A5 gene |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520332478 |
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