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From the Department of Internal Medicine, University Hospital of Lausanne, Switzerland (P.A., P.M.-V., G.W., P.V.); Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Switzerland (J.V., S.P., N.S., F. Montecucco, N.V.); Department of Human Protein Sciences, Faculty of Medicine, (J.V., S.P., N.S., N.V.), Department of Pathology and Immunology, Faculty of Medicine (O.H.), and Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties (F. Montecucco, F. Mach), University of Geneva, Switzerland; First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Italy (F. Montecucco); Institute of Social and Preventive Medicine, University Hospital of Lausanne, Switzerland (Z.K.); and Swiss Institute of Bioinformatics, Lausanne, Switzerland (Z.K.).
Published: December 2017
AI Article Synopsis
Article Abstract
Objective: We aimed to determine whether autoantibodies against apoA-1 (apolipoprotein A-1; anti-apoA-1 IgG) predict incident coronary artery disease (CAD), defined as adjudicated incident myocardial infarction, angina, percutaneous coronary revascularization, or bypass grafting, in the general population. We further investigated whether this association is modulated by a functional CD14 receptor single nucleotide polymorphism.
Approach And Results: In a prospectively studied, population-based cohort of 5220 subjects (mean age 52.6±10.7 years, 47.4% males), followed over a median period of 5.6 years, subjects positive versus negative for anti-apoA-1 IgG presented a total CAD rate of 3.9% versus 2.8% (=0.077) and a nonfatal CAD rate of 3.6% versus 2.3% (=0.018), respectively. After multivariate adjustment for established cardiovascular risk factors, the hazard ratios of anti-apoA-1 IgG for total and nonfatal CAD were: hazard ratio=1.36 (95% confidence interval, 0.94-1.97; =0.105) and hazard ratio=1.53 (95% confidence interval, 1.03-2.26; =0.034), respectively. In subjects with available genetic data for the C260T single nucleotide polymorphism in the CD14 receptor gene (n=4247), we observed a significant interaction between anti-apoA-1 IgG and allele status with regards to CAD risk, with anti-apoA-1 IgG conferring the highest risk for total and nonfatal CAD in non-TT carriers, whereas being associated with the lowest risk for total and nonfatal CAD in TT homozygotes ( for interaction =0.011 and for interaction =0.033, respectively).
Conclusions: Anti-apoA-1 IgG are independent predictors of nonfatal incident CAD in the general population. The strength of this association is dependent on a functional polymorphism of the CD14 receptor gene, a finding suggesting a gene-autoantibody interaction for the development of CAD.
