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=Volume 8 - 2017

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=Background: 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
possible genetic determinants have not been studied.
Objective: 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).
Methods: Clinical, biological and genetic data from the population-based, prospective CoLaus study, including 5220 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.
Results: 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 standard deviation 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 9 SNPs belonging to the Fc receptor like-3 (FCRL3) gene that 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.
Conclusion: 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.