Anti-Apolipoprotein A-1 IgG Predict All-Cause Mortality and Are Associated with Fc Receptor-Like 3 Polymorphisms.
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2017
- doi: 10.3389/fimmu.2017.00437
- issn: 1664-3224
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Patients--Mortality Mortality, Law of IgGCiter ce document
P. Antiochos et al., « Anti-Apolipoprotein A-1 IgG Predict All-Cause Mortality and Are Associated with Fc Receptor-Like 3 Polymorphisms. », Serveur académique Lausannois, ID : 10.3389/fimmu.2017.00437
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Résumé
Autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) have emerged as an independent biomarker for cardiovascular disease and mortality. However, their association with all-cause mortality in the community, as well as their genetic determinants, have not been studied. To determine whether anti-apoA-1 IgG: (a) predict all-cause mortality in the general population and (b) are associated with single-nucleotide polymorphisms (SNPs) in a genome-wide association study (GWAS). Clinical, biological, and genetic data were obtained from the population-based, prospective CoLaus study, including 5,220 participants (mean age 52.6 years, 47.3% men) followed over a median duration of 5.6 years. The primary study outcome was all-cause mortality. After multivariate adjustment, anti-apoA-1 IgG positivity independently predicted all-cause mortality: hazard ratio (HR) = 1.54, 95% confidence interval (95% CI): 1.11-2.13, P = 0.01. A dose-effect relationship was also observed, each SD of logarithmically transformed anti-apoA-1 IgG being associated with a 15% increase in mortality risk: HR = 1.15, 95% CI: 1.02-1.28, P = 0.028. The GWAS yielded nine SNPs belonging to the Fc receptor-like 3 (FCRL3) gene, which were significantly associated with anti-apoA-1 IgG levels, with the lead SNP (rs6427397, P = 1.54 × 10(-9)) explaining 0.67% of anti-apoA-1 IgG level variation. Anti-apoA-1 IgG levels (a) independently predict all-cause mortality in the general population and (b) are linked to FCRL3, a susceptibility gene for numerous autoimmune diseases. Our findings indicate that preclinical autoimmunity to anti-apoA-1 IgG may represent a novel mortality risk factor.