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USF1 gene variants, cardiovascular risk, and mortality in European Americans: analysis of two US cohort studies.
Tuesday,2012-11-06 12:09 America/Los_Angeles — eenright
| Title | USF1 gene variants, cardiovascular risk, and mortality in European Americans: analysis of two US cohort studies. |
| Publication Type | Journal Article |
| Year of Publication | 2007 |
| Authors | Reiner, AP, Carlson, CS, Jenny, NS, J Durda, P, Siscovick, DS, Nickerson, DA, Tracy, RP |
| Journal | Arterioscler Thromb Vasc Biol |
| Volume | 27 |
| Issue | 12 |
| Pagination | 2736-42 |
| Date Published | 2007 Dec |
| ISSN | 1524-4636 |
| Keywords | Adult, Age Factors, Aged, Aged, 80 and over, Aging, Blood Glucose, C-Reactive Protein, Calcium, Cardiovascular Diseases, Carotid Artery, Common, Cohort Studies, Coronary Artery Disease, Coronary Vessels, European Continental Ancestry Group, Female, Follow-Up Studies, Genetic Predisposition to Disease, Humans, Hyperlipidemia, Familial Combined, Insulin, Interleukin-6, Linkage Disequilibrium, Lipids, Male, Odds Ratio, Phenotype, Polymorphism, Single Nucleotide, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States, Upstream Stimulatory Factors |
| Abstract | <p><b>OBJECTIVE: </b>A common haplotype of the upstream transcription factor 1 gene (USF1) has been associated with decreased susceptibility to familial combined hyperlipidemia (FCHL) and, paradoxically, with increased risk of cardiovascular disease (CVD) and all-cause mortality.</p><p><b>METHODS AND RESULTS: </b>We assessed associations between USF1 tagSNPs, CVD risk factors, and aging-related phenotypes using data from 2 large population-based cohorts, Coronary Artery Risk Development in Young Adults (CARDIA) and the Cardiovascular Health Study (CHS), comprising younger and older adults, respectively. In CARDIA, each additional copy of the FCHL low-risk allele was associated with 2.4 mg/dL lower levels of LDL cholesterol (P=0.01) and decreased risk of subclinical atherosclerosis as assessed by coronary artery calcium (odds ratio 0.79; 95%CI 0.63 to 0.98). Whereas there was little association between USF1 genotype and metabolic or CVD traits in older adults from CHS, the USF1 low-risk dyslipidemia allele was associated with higher plasma C-reactive protein and interleukin (IL)-6 levels and with increased risk of mortality, particularly attributable to noncardiovascular causes.</p><p><b>CONCLUSIONS: </b>There appears to be a complex and possibly age-dependent relationship between USF1 genotype, atherosclerosis phenotypes, and CVD risk. USF1 may influence mortality through pathways distinct from atherosclerosis. Alternatively, linkage disequilibrium with neighboring polymorphisms in other genes such as F11R may be responsible for the observed USF1 genotype-phenotype associations in older adults.</p> |
| DOI | 10.1161/ATVBAHA.107.154559 |
| Alternate Journal | Arterioscler Thromb Vasc Biol |
| PubMed ID | 17885212 |
| Grant List | HL066642 / HL / NHLBI NIH HHS / United States HL066682 / HL / NHLBI NIH HHS / United States HL071017 / HL / NHLBI NIH HHS / United States N01 HC-15103 / HC / NHLBI NIH HHS / United States N01-HC-05187 / HC / NHLBI NIH HHS / United States N01-HC-35129 / HC / NHLBI NIH HHS / United States N01-HC-45133 / HC / NHLBI NIH HHS / United States N01-HC-45134 / HC / NHLBI NIH HHS / United States N01-HC-48047 / HC / NHLBI NIH HHS / United States N01-HC-48048 / HC / NHLBI NIH HHS / United States N01-HC-48049 / HC / NHLBI NIH HHS / United States N01-HC-48050 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01-HC-95095 / HC / NHLBI NIH HHS / United States R01 HL-071862-03 / HL / NHLBI NIH HHS / United States U19AG023122 / AG / NIA NIH HHS / United States |