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
Department of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland.
Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland.
Front Immunol. 2017 Apr 18;8:437. doi: 10.3389/fimmu.2017.00437. eCollection 2017.
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, = 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, = 0.028. The GWAS yielded nine SNPs belonging to the Fc receptor-like 3 () gene, which were significantly associated with anti-apoA-1 IgG levels, with the lead SNP (rs6427397, = 1.54 × 10) 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 , 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.
抗载脂蛋白A-1自身抗体（抗载脂蛋白A-1 IgG）已成为心血管疾病和死亡率的独立生物标志物。然而，它们与社区全因死亡率的关联以及遗传决定因素尚未得到研究。
确定抗载脂蛋白A-1 IgG是否：（a）预测普通人群的全因死亡率，以及（b）在全基因组关联研究（GWAS）中与单核苷酸多态性（SNP）相关。
从基于人群的前瞻性CoLaus研究中获取临床、生物学和遗传数据，该研究包括5220名参与者（平均年龄52.6岁，47.3%为男性），随访中位时间为5.6年。主要研究结局为全因死亡率。
经过多变量调整后，抗载脂蛋白A-1 IgG阳性独立预测全因死亡率：风险比（HR）=1.54，95%置信区间（95%CI）：1.11 - 2.13，P = 0.01。还观察到剂量效应关系，对数转换后的抗载脂蛋白A-1 IgG每增加一个标准差，死亡风险增加15%：HR = 1.15，95%CI：1.02 - 1.28，P = 0.028。GWAS产生了9个属于Fc受体样3（FCRL3）基因的SNP，它们与抗载脂蛋白A-1 IgG水平显著相关，其中主要SNP（rs6427397，P = 1.54 × 10⁻⁸）解释了抗载脂蛋白A-1 IgG水平变异的0.67%。
抗载脂蛋白A-1 IgG水平（a）独立预测普通人群的全因死亡率，（b）与FCRL3相关，FCRL3是多种自身免疫性疾病的易感基因。我们的研究结果表明，针对抗载脂蛋白A-1 IgG的临床前自身免疫可能是一种新的死亡风险因素。
