Genetic variants from lipid-related pathways and risk for incident myocardial infarction.
<h4>Background</h4>Circulating lipids levels, as well as several familial lipid metabolism disorders, are strongly associated with initiation and progression of atherosclerosis and incidence of myocardial infarction (MI).<h4>Objectives</h4>We hypothesized that genetic variant...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0060454&type=printable |
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| _version_ | 1849434207469699072 |
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| author | Ci Song Nancy L Pedersen Chandra A Reynolds Maria Sabater-Lleal Stavroula Kanoni Christina Willenborg CARDIoGRAMplusC4D Consortium Ann-Christine Syvänen Hugh Watkins Anders Hamsten Jonathan A Prince Erik Ingelsson |
| author_facet | Ci Song Nancy L Pedersen Chandra A Reynolds Maria Sabater-Lleal Stavroula Kanoni Christina Willenborg CARDIoGRAMplusC4D Consortium Ann-Christine Syvänen Hugh Watkins Anders Hamsten Jonathan A Prince Erik Ingelsson |
| author_sort | Ci Song |
| collection | DOAJ |
| description | <h4>Background</h4>Circulating lipids levels, as well as several familial lipid metabolism disorders, are strongly associated with initiation and progression of atherosclerosis and incidence of myocardial infarction (MI).<h4>Objectives</h4>We hypothesized that genetic variants associated with circulating lipid levels would also be associated with MI incidence, and have tested this in three independent samples.<h4>Setting and subjects</h4>Using age- and sex-adjusted additive genetic models, we analyzed 554 single nucleotide polymorphisms (SNPs) in 41 candidate gene regions proposed to be involved in lipid-related pathways potentially predisposing to incidence of MI in 2,602 participants of the Swedish Twin Register (STR; 57% women). All associations with nominal P<0.01 were further investigated in the Uppsala Longitudinal Study of Adult Men (ULSAM; N = 1,142).<h4>Results</h4>In the present study, we report associations of lipid-related SNPs with incident MI in two community-based longitudinal studies with in silico replication in a meta-analysis of genome-wide association studies. Overall, there were 9 SNPs in STR with nominal P-value <0.01 that were successfully genotyped in ULSAM. rs4149313 located in ABCA1 was associated with MI incidence in both longitudinal study samples with nominal significance (hazard ratio, 1.36 and 1.40; P-value, 0.004 and 0.015 in STR and ULSAM, respectively). In silico replication supported the association of rs4149313 with coronary artery disease in an independent meta-analysis including 173,975 individuals of European descent from the CARDIoGRAMplusC4D consortium (odds ratio, 1.03; P-value, 0.048).<h4>Conclusions</h4>rs4149313 is one of the few amino acid changing variants in ABCA1 known to associate with reduced cholesterol efflux. Our results are suggestive of a weak association between this variant and the development of atherosclerosis and MI. |
| format | Article |
| id | doaj-art-a0dc0fd162404154828ba5c8ea54efb3 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-a0dc0fd162404154828ba5c8ea54efb32025-08-20T03:26:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e6045410.1371/journal.pone.0060454Genetic variants from lipid-related pathways and risk for incident myocardial infarction.Ci SongNancy L PedersenChandra A ReynoldsMaria Sabater-LlealStavroula KanoniChristina WillenborgCARDIoGRAMplusC4D ConsortiumAnn-Christine SyvänenHugh WatkinsAnders HamstenJonathan A PrinceErik Ingelsson<h4>Background</h4>Circulating lipids levels, as well as several familial lipid metabolism disorders, are strongly associated with initiation and progression of atherosclerosis and incidence of myocardial infarction (MI).<h4>Objectives</h4>We hypothesized that genetic variants associated with circulating lipid levels would also be associated with MI incidence, and have tested this in three independent samples.<h4>Setting and subjects</h4>Using age- and sex-adjusted additive genetic models, we analyzed 554 single nucleotide polymorphisms (SNPs) in 41 candidate gene regions proposed to be involved in lipid-related pathways potentially predisposing to incidence of MI in 2,602 participants of the Swedish Twin Register (STR; 57% women). All associations with nominal P<0.01 were further investigated in the Uppsala Longitudinal Study of Adult Men (ULSAM; N = 1,142).<h4>Results</h4>In the present study, we report associations of lipid-related SNPs with incident MI in two community-based longitudinal studies with in silico replication in a meta-analysis of genome-wide association studies. Overall, there were 9 SNPs in STR with nominal P-value <0.01 that were successfully genotyped in ULSAM. rs4149313 located in ABCA1 was associated with MI incidence in both longitudinal study samples with nominal significance (hazard ratio, 1.36 and 1.40; P-value, 0.004 and 0.015 in STR and ULSAM, respectively). In silico replication supported the association of rs4149313 with coronary artery disease in an independent meta-analysis including 173,975 individuals of European descent from the CARDIoGRAMplusC4D consortium (odds ratio, 1.03; P-value, 0.048).<h4>Conclusions</h4>rs4149313 is one of the few amino acid changing variants in ABCA1 known to associate with reduced cholesterol efflux. Our results are suggestive of a weak association between this variant and the development of atherosclerosis and MI.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0060454&type=printable |
| spellingShingle | Ci Song Nancy L Pedersen Chandra A Reynolds Maria Sabater-Lleal Stavroula Kanoni Christina Willenborg CARDIoGRAMplusC4D Consortium Ann-Christine Syvänen Hugh Watkins Anders Hamsten Jonathan A Prince Erik Ingelsson Genetic variants from lipid-related pathways and risk for incident myocardial infarction. PLoS ONE |
| title | Genetic variants from lipid-related pathways and risk for incident myocardial infarction. |
| title_full | Genetic variants from lipid-related pathways and risk for incident myocardial infarction. |
| title_fullStr | Genetic variants from lipid-related pathways and risk for incident myocardial infarction. |
| title_full_unstemmed | Genetic variants from lipid-related pathways and risk for incident myocardial infarction. |
| title_short | Genetic variants from lipid-related pathways and risk for incident myocardial infarction. |
| title_sort | genetic variants from lipid related pathways and risk for incident myocardial infarction |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0060454&type=printable |
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