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Fetuin-A and risk of coronary heart disease: A Mendelian randomization analysis and a pooled analysis of AHSG genetic variants in 7 prospective studies.
Tuesday,2015-10-06 13:50 America/Los_Angeles — zdrager
| Title | Fetuin-A and risk of coronary heart disease: A Mendelian randomization analysis and a pooled analysis of AHSG genetic variants in 7 prospective studies. |
| Publication Type | Journal Article |
| Year of Publication | 2015 |
| Authors | Laugsand, LE, Ix, JH, Bartz, TM, Djoussé, L, Kizer, JR, Tracy, RP, Dehghan, A, Rexrode, K, Lopez, OL, Rimm, EB, Siscovick, DS, O'Donnell, CJ, Newman, A, Mukamal, KJ, Jensen, MK |
| Journal | Atherosclerosis |
| Volume | 243 |
| Issue | 1 |
| Pagination | 44-52 |
| Date Published | 2015 Nov |
| ISSN | 1879-1484 |
| Keywords | Aged, Aged, 80 and over, alpha-2-HS-Glycoprotein, Carotid Intima-Media Thickness, Coronary Vessels, Female, Genetic Variation, Genotype, Heart Diseases, Humans, Insulin Resistance, Longitudinal Studies, Male, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Prospective Studies, Risk Factors, Vascular Calcification |
| Abstract | <p><b>BACKGROUND AND AIMS: </b>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).</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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).</p><p><b>CONCLUSION: </b>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.</p> |
| DOI | 10.1016/j.atherosclerosis.2015.08.031 |
| Alternate Journal | Atherosclerosis |
| PubMed ID | 26343871 |
| PubMed Central ID | PMC4609621 |
| Grant List | 1R01AG032098-01A1 / AG / NIA NIH HHS / United States 268200625226C / / PHS HHS / United States 268200800007C / / PHS HHS / United States 268201100005C / / PHS HHS / United States 268201100006C / / PHS HHS / United States 268201100007C / / PHS HHS / United States 268201100008C / / PHS HHS / United States 268201100009C / / PHS HHS / United States 268201100010C / / PHS HHS / United States 268201100011C / / PHS HHS / United States 268201100012C / / PHS HHS / United States 268201200036C / / PHS HHS / United States CA55075 / CA / NCI NIH HHS / United States CA87969 / CA / NCI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States HL080295 / HL / NHLBI NIH HHS / United States HL34594 / HL / NHLBI NIH HHS / United States HL35464 / HL / NHLBI NIH HHS / United States N01-AG-12100 / AG / NIA NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States N01AG62101 / AG / NIA NIH HHS / United States N01AG62103 / AG / NIA NIH HHS / United States N01AG62106 / AG / NIA NIH HHS / United States N01HC55222 / HC / NHLBI NIH HHS / United States N01HC65226 / HC / NHLBI NIH HHS / United States N01HC65226 / HL / NHLBI NIH HHS / United States N01HC85079 / HC / NHLBI NIH HHS / United States N01HC85080 / HC / NHLBI NIH HHS / United States N01HC85081 / HC / NHLBI NIH HHS / United States N01HC85082 / HC / NHLBI NIH HHS / United States N01HC85083 / HC / NHLBI NIH HHS / United States N01HC85086 / HC / NHLBI NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States R01 HL094555 / HL / NHLBI NIH HHS / United States R01 HL094555 / HL / NHLBI NIH HHS / United States R01AG023629 / AG / NIA NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States |