AUTHOR=Antiochos Panagiotis , Marques-Vidal Pedro , Virzi Julien , Pagano Sabrina , Satta Nathalie , Hartley Oliver , Montecucco Fabrizio , Mach François , Kutalik Zoltán , Waeber Gerard , Vollenweider Peter , Vuilleumier Nicolas 

TITLE=Anti-Apolipoprotein A-1 IgG Predict All-Cause Mortality and Are Associated with Fc Receptor-Like 3 Polymorphisms

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00437

DOI=10.3389/fimmu.2017.00437

ISSN=1664-3224

ABSTRACT=<sec id="ST1"><title>Background</title><p>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.</p></sec><sec id="ST2"><title>Objective</title><p>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).</p></sec><sec id="ST3"><title>Methods</title><p>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.</p></sec><sec id="ST4"><title>Results</title><p>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, <italic>P</italic> = 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, <italic>P</italic> = 0.028. The GWAS yielded nine SNPs belonging to the Fc receptor-like 3 (<italic>FCRL3</italic>) gene, which were significantly associated with anti-apoA-1 IgG levels, with the lead SNP (rs6427397, <italic>P</italic> = 1.54 × 10<sup>−9</sup>) explaining 0.67% of anti-apoA-1 IgG level variation.</p></sec><sec id="ST5"><title>Conclusion</title><p>Anti-apoA-1 IgG levels (a) independently predict all-cause mortality in the general population and (b) are linked to <italic>FCRL3</italic>, 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.</p></sec>