{
    "abstract": "The aim of this study was to assess the influence of pro-inflammatory interleukin (IL)-1 genotype status on the risk for coronary artery disease (CAD), defined as >50% diameter stenosis, and cardiovascular events mediated by oxidized phospholipids (OxPLs) and lipoprotein (Lp) (a).\nOxPLs are pro-inflammatory, circulate on Lp(a), and mediate CAD. Genetic variations in the IL-1 region are associated with increased inflammatory mediators.\nIL-1 genotypes, OxPL on apolipoprotein B-100 (OxPL/apoB), and Lp(a) levels were measured in 499 patients undergoing coronary angiography. The composite genotype termed IL-1(+) was defined by 3 single-nucleotide polymorphisms in the IL-1 gene cluster associated with higher levels of pro-inflammatory cytokines. All other IL-1 genotypes were termed IL-1(-).\nAmong IL-1(+) patients, the highest quartile of OxPL/apoB was significantly associated with a higher risk for CAD compared with the lowest quartile (odds ratio [OR]: 2.84; p = 0.001). This effect was accentuated in patients age \u226460 years (OR: 7.03; p < 0.001). In IL-1(-) patients, OxPL/apoB levels showed no association with CAD. The interaction was significant for OxPL/apoB (OR: 1.99; p = 0.004) and Lp(a) (OR: 1.96; p < 0.001) in the IL-1(+) group versus the IL-1(-) group in patients age \u226460 years but not in those age >60 years. In IL-1(+) patients age \u226460 years, after adjustment for established risk factors, high-sensitivity C-reactive protein, and Lp(a), OxPL/apoB remained an independent predictor of CAD. IL-1(+) patients above the median OxPL/apoB presented to the cardiac catheterization laboratory a mean of 3.9 years earlier (p = 0.002) and had worse 4-year event-free survival (death, myocardial infarction, stroke, and need for revascularization) compared with other groups (p = 0.006).\nOur study suggests that IL-1 genotype status can stratify population risk for CAD and cardiovascular events mediated by OxPL. These data suggest a clinically relevant biological link between pro-inflammatory IL-1 genotype, oxidation of phospholipids, Lp(a), and genetic predisposition to CAD and cardiovascular events.",
    "authors": [
        {
            "affiliation": "Division of Cardiovascular Diseases, University of California San Diego, La Jolla, California. Electronic address: stsimikas@ucsd.edu.",
            "firstname": "Sotirios",
            "initials": "S",
            "lastname": "Tsimikas"
        },
        {
            "affiliation": "Division of Genomic Medicine, University of Sheffield, Sheffield, United Kingdom.",
            "firstname": "Gordon W",
            "initials": "GW",
            "lastname": "Duff"
        },
        {
            "affiliation": "Department of Cardiology, Geisinger Health System, Danville, Pennsylvania.",
            "firstname": "Peter B",
            "initials": "PB",
            "lastname": "Berger"
        },
        {
            "affiliation": "Interleukin Genetics, Inc., Waltham, Massachusetts.",
            "firstname": "John",
            "initials": "J",
            "lastname": "Rogus"
        },
        {
            "affiliation": "Interleukin Genetics, Inc., Waltham, Massachusetts.",
            "firstname": "Kenneth",
            "initials": "K",
            "lastname": "Huttner"
        },
        {
            "affiliation": "Veterans Affairs Medical Center, San Diego, California.",
            "firstname": "Paul",
            "initials": "P",
            "lastname": "Clopton"
        },
        {
            "affiliation": "Veterans Affairs North Texas Healthcare System, Dallas, Texas.",
            "firstname": "Emmanuel",
            "initials": "E",
            "lastname": "Brilakis"
        },
        {
            "affiliation": "Interleukin Genetics, Inc., Waltham, Massachusetts.",
            "firstname": "Kenneth S",
            "initials": "KS",
            "lastname": "Kornman"
        },
        {
            "affiliation": "Division of Endocrinology and Metabolism, University of California San Diego, La Jolla, California.",
            "firstname": "Joseph L",
            "initials": "JL",
            "lastname": "Witztum"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.",
    "doi": "10.1016/j.jacc.2013.12.030",
    "journal": "Journal of the American College of Cardiology",
    "keywords": [
        "IL-1",
        "atherosclerosis",
        "genetic risk stratification",
        "haplotype",
        "inflammation",
        "lipoprotein(a)",
        "lipoproteins",
        "oxidation",
        "oxidized phospholipids",
        "polymorphism"
    ],
    "methods": null,
    "publication_date": "2014-02-18",
    "pubmed_id": "24530664\n21252151\n2567438\n18490534\n22850787\n18240545\n16399797\n11991668\n15539626\n18451331\n18369665\n22768033\n22072054\n20709104\n18703194\n19811432\n17981284\n19574724\n15051633\n8696938\n10027806\n22425140\n12824054\n16131798\n11127457\n17413037\n21982649\n22935534\n22969153\n23541965\n12575961\n15184281\n17541022\n23122790\n20828647\n22003918\n22497821\n16000355\n1301918\n11145356\n9710237\n16470016\n11076651\n15777561\n16036505\n12454835\n21248262\n17443229\n22744645\n11073843\n22634325\n11145356\n10637274\n15939811\n12615675\n9462524\n15059807\n18474811\n16414045\n16456091\n21737788\n21925592\n11751881\n12193156\n18716798\n23828779\n7679504\n21935443\n21179199\n16000355\n18061193\n17093289\n22003918\n1301918\n16399797\n18369665",
    "results": "Among IL-1(+) patients, the highest quartile of OxPL/apoB was significantly associated with a higher risk for CAD compared with the lowest quartile (odds ratio [OR]: 2.84; p = 0.001). This effect was accentuated in patients age \u226460 years (OR: 7.03; p < 0.001). In IL-1(-) patients, OxPL/apoB levels showed no association with CAD. The interaction was significant for OxPL/apoB (OR: 1.99; p = 0.004) and Lp(a) (OR: 1.96; p < 0.001) in the IL-1(+) group versus the IL-1(-) group in patients age \u226460 years but not in those age >60 years. In IL-1(+) patients age \u226460 years, after adjustment for established risk factors, high-sensitivity C-reactive protein, and Lp(a), OxPL/apoB remained an independent predictor of CAD. IL-1(+) patients above the median OxPL/apoB presented to the cardiac catheterization laboratory a mean of 3.9 years earlier (p = 0.002) and had worse 4-year event-free survival (death, myocardial infarction, stroke, and need for revascularization) compared with other groups (p = 0.006).",
    "title": "Pro-inflammatory interleukin-1 genotypes potentiate the risk of coronary artery disease and cardiovascular events mediated by oxidized phospholipids and lipoprotein(a).",
    "xml": "<Element 'PubmedArticle' at 0x7885046070b0>"
}