期刊
ATHEROSCLEROSIS
卷 243, 期 1, 页码 44-52出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2015.08.031
关键词
Fetuin-A; Single nucleotide polymorphisms; Coronary heart disease; Mendelian randomization; Meta-analysis
资金
- National Heart, Lung, and Blood Institute (NHLBI) [R01 HL094555]
- NHLBI CARe project (Broad Institute of Massachusetts Institute of Technology and Harvard) [N01HC65226]
- NHLBI [HL080295]
- National Institute on Aging (NIA) [R01AG023629]
- Liaison Committee
- National Institutes of Health, Bethesda, MD [HL35464, CA55075, CA87969, HL34594]
- NIH [N01-AG-12100]
- NIA Intramural Research Program
- Althingi (the Icelandic Parliament)
- National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]
- National Human Genome Research Institute [U01HG004402]
- National Institutes of Health [HHSN268200625226C]
- National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]
- Affymetrix, Inc [N02-HL-6-4278]
- Netherlands Organization for Scientific Research (NWO) [916.12.154]
- EUR Fellowship
- Erasmus University Rotterdam
- Netherlands Organization for Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly (RIDE)
- Netherlands Heart Foundation
- Ministry of Education, Culture and Science
- Ministry of Health Welfare and Sports
- European Commission
- Municipality of Rotterdam
- Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]
- National Institutes of Aging
- NIA [N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1]
- Hjartavernd (the Icelandic Heart Association)
- Erasmus Medical Center
- [HHSN268201200036C]
- [HHSN268200800007C]
- [N01HC55222]
- [N01HC85079]
- [N01HC85080]
- [N01HC85081]
- [N01HC85082]
- [N01HC85083]
- [NO1HC85086]
Background and aims: Fetuin-A has a plausible role in the inhibition of arterial calcification, but its association with risk of coronary heart disease (CHD) in the general population is unclear. We used two common genetic variants in the fetuin-A gene (AHSG) that are strongly associated with circulating fetuin-A levels to investigate the associations with risk of CHD and subclinical cardiovascular measures (intima-media thickness, ankle-arm index, and coronary artery calcification). Methods: Genetic variation and fetuin-A levels were assessed in 3299 community-living individuals (2733 Caucasians and 566 African Americans) 65 years of age or older, free of previous cardiovascular disease, who participated in the Cardiovascular Health Study (CHS) in 1992-1993. Results: Among Caucasians, both rs2248690 and rs4917 were associated with 12% lower fetuin-A concentrations per minor allele (P < 0.0001). The hazard ratios (HRs) per minor allele for incident CHD were 1.12 (95% CI: 1.00-1.26) for rs2248690 and 1.02 (0.91-1.14) for rs4917. Using both genotypes as an instrumental variable for measured fetuin-A, the HRs for one standard deviation increase in genetically determined fetuin-A levels on CHD risk were 0.84 (95% CI: 0.70-1.00) for rs2248690 and 0.97 (95% CI: 0.82-1.14) for rs4917, respectively. However, in CHS neither of the genotypes were associated with subclinical cardiovascular measures and when CHS data were meta-analyzed with data from six other prospective studies (totaling 26,702 Caucasian participants and 3295 CHD cases), the meta-analyzed HRs for incident CHD were 1.12 (0.93-1.34) and 1.06 (0.93-1.20) for rs2248690 and rs4917, respectively (p heterogeneity 0.005 and 0.0048). Conclusion: Common variants in the AHSG gene are strongly associated with fetuin-A levels, but their concurrent association with CHD risk in current prospective studies is inconsistent. Further investigation in studies with measured fetuin-A and AHSG variants is needed to clarify the potential causal association of fetuin-A with CHD risk. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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