<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Stitziel, Nathan O</style></author><author><style face="normal" font="default" size="100%">Khera, Amit V</style></author><author><style face="normal" font="default" size="100%">Wang, Xiao</style></author><author><style face="normal" font="default" size="100%">Bierhals, Andrew J</style></author><author><style face="normal" font="default" size="100%">Vourakis, A Christina</style></author><author><style face="normal" font="default" size="100%">Sperry, Alexandra E</style></author><author><style face="normal" font="default" size="100%">Natarajan, Pradeep</style></author><author><style face="normal" font="default" size="100%">Klarin, Derek</style></author><author><style face="normal" font="default" size="100%">Emdin, Connor A</style></author><author><style face="normal" font="default" size="100%">Zekavat, Seyedeh M</style></author><author><style face="normal" font="default" size="100%">Nomura, Akihiro</style></author><author><style face="normal" font="default" size="100%">Erdmann, Jeanette</style></author><author><style face="normal" font="default" size="100%">Schunkert, Heribert</style></author><author><style face="normal" font="default" size="100%">Samani, Nilesh J</style></author><author><style face="normal" font="default" size="100%">Kraus, William E</style></author><author><style face="normal" font="default" size="100%">Shah, Svati H</style></author><author><style face="normal" font="default" size="100%">Yu, Bing</style></author><author><style face="normal" font="default" size="100%">Boerwinkle, Eric</style></author><author><style face="normal" font="default" size="100%">Rader, Daniel J</style></author><author><style face="normal" font="default" size="100%">Gupta, Namrata</style></author><author><style face="normal" font="default" size="100%">Frossard, Philippe M</style></author><author><style face="normal" font="default" size="100%">Rasheed, Asif</style></author><author><style face="normal" font="default" size="100%">Danesh, John</style></author><author><style face="normal" font="default" size="100%">Lander, Eric S</style></author><author><style face="normal" font="default" size="100%">Gabriel, Stacey</style></author><author><style face="normal" font="default" size="100%">Saleheen, Danish</style></author><author><style face="normal" font="default" size="100%">Musunuru, Kiran</style></author><author><style face="normal" font="default" size="100%">Kathiresan, Sekar</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">PROMIS and Myocardial Infarction Genetics Consortium Investigators</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">ANGPTL3 Deficiency and Protection Against Coronary Artery Disease.</style></title><secondary-title><style face="normal" font="default" size="100%">J Am Coll Cardiol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">J Am Coll Cardiol</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">Angiopoietin-Like Protein 3</style></keyword><keyword><style  face="normal" font="default" size="100%">Angiopoietin-like Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Angiopoietins</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Atherosclerosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Case-Control Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Coronary Artery Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Lipids</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Inbred C57BL</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Knockout</style></keyword><keyword><style  face="normal" font="default" size="100%">Middle Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutation, Missense</style></keyword><keyword><style  face="normal" font="default" size="100%">Myocardial Infarction</style></keyword><keyword><style  face="normal" font="default" size="100%">Risk Factors</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2017 Apr 25</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">69</style></volume><pages><style face="normal" font="default" size="100%">2054-2063</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;Familial combined hypolipidemia, a Mendelian condition characterized by substantial reductions in all 3 major lipid fractions, is caused by mutations that inactivate the gene angiopoietin-like 3 (ANGPTL3). Whether ANGPTL3 deficiency reduces risk of coronary artery disease (CAD) is unknown.&lt;/p&gt;&lt;p&gt;&lt;b&gt;OBJECTIVES: &lt;/b&gt;The study goal was to leverage 3 distinct lines of evidence-a family that included individuals with complete (compound heterozygote) ANGPTL3 deficiency, a population based-study of humans with partial (heterozygote) ANGPTL3 deficiency, and biomarker levels in patients with myocardial infarction (MI)-to test whether ANGPTL3 deficiency is associated with lower risk for CAD.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;We assessed coronary atherosclerotic burden in 3 individuals with complete ANGPTL3 deficiency and 3 wild-type first-degree relatives using computed tomography angiography. In the population, ANGPTL3 loss-of-function (LOF) mutations were ascertained in up to 21,980 people with CAD and 158,200 control subjects. LOF mutations were defined as nonsense, frameshift, and splice-site variants, along with missense variants resulting in &lt;25% of wild-type ANGPTL3 activity in a mouse model. In a biomarker study, circulating ANGPTL3 concentration was measured in 1,493 people who presented with MI and 3,232 control subjects.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;The 3 individuals with complete ANGPTL3 deficiency showed no evidence of coronary atherosclerotic plaque. ANGPTL3 gene sequencing demonstrated that approximately 1 in 309 people was a heterozygous carrier for an LOF mutation. Compared with those without mutation, heterozygous carriers of ANGPTL3 LOF mutations demonstrated a 17% reduction in circulating triglycerides and a 12% reduction in low-density lipoprotein cholesterol. Carrier status was associated with a 34% reduction in odds of CAD (odds ratio: 0.66; 95% confidence interval: 0.44 to 0.98; p = 0.04). Individuals in the lowest tertile of circulating ANGPTL3 concentrations, compared with the highest, had reduced odds of MI (adjusted odds ratio: 0.65; 95% confidence interval: 0.55 to 0.77; p &lt; 0.001).&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;ANGPTL3 deficiency is associated with protection from CAD.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">16</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/28385496?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Kim-Hellmuth, Sarah</style></author><author><style face="normal" font="default" size="100%">Bechheim, Matthias</style></author><author><style face="normal" font="default" size="100%">Pütz, Benno</style></author><author><style face="normal" font="default" size="100%">Mohammadi, Pejman</style></author><author><style face="normal" font="default" size="100%">Nédélec, Yohann</style></author><author><style face="normal" font="default" size="100%">Giangreco, Nicholas</style></author><author><style face="normal" font="default" size="100%">Becker, Jessica</style></author><author><style face="normal" font="default" size="100%">Kaiser, Vera</style></author><author><style face="normal" font="default" size="100%">Fricker, Nadine</style></author><author><style face="normal" font="default" size="100%">Beier, Esther</style></author><author><style face="normal" font="default" size="100%">Boor, Peter</style></author><author><style face="normal" font="default" size="100%">Castel, Stephane E</style></author><author><style face="normal" font="default" size="100%">Nöthen, Markus M</style></author><author><style face="normal" font="default" size="100%">Barreiro, Luis B</style></author><author><style face="normal" font="default" size="100%">Pickrell, Joseph K</style></author><author><style face="normal" font="default" size="100%">Müller-Myhsok, Bertram</style></author><author><style face="normal" font="default" size="100%">Lappalainen, Tuuli</style></author><author><style face="normal" font="default" size="100%">Schumacher, Johannes</style></author><author><style face="normal" font="default" size="100%">Hornung, Veit</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Genetic regulatory effects modified by immune activation contribute to autoimmune disease associations.</style></title><secondary-title><style face="normal" font="default" size="100%">Nat Commun</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Nat Commun</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Acetylmuramyl-Alanyl-Isoglutamine</style></keyword><keyword><style  face="normal" font="default" size="100%">Adjuvants, Immunologic</style></keyword><keyword><style  face="normal" font="default" size="100%">Adolescent</style></keyword><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">Autoimmune Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Profiling</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Regulation</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Predisposition to Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Healthy Volunteers</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Indicators and Reagents</style></keyword><keyword><style  face="normal" font="default" size="100%">Lipids</style></keyword><keyword><style  face="normal" font="default" size="100%">Lipopolysaccharides</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Monocytes</style></keyword><keyword><style  face="normal" font="default" size="100%">Quantitative Trait Loci</style></keyword><keyword><style  face="normal" font="default" size="100%">Regulatory Sequences, Nucleic Acid</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA, Double-Stranded</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA, Messenger</style></keyword><keyword><style  face="normal" font="default" size="100%">Young Adult</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2017 Aug 16</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">8</style></volume><pages><style face="normal" font="default" size="100%">266</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;The immune system plays a major role in human health and disease, and understanding genetic causes of interindividual variability of immune responses is vital. Here, we isolate monocytes from 134 genotyped individuals, stimulate these cells with three defined microbe-associated molecular patterns (LPS, MDP, and 5'-ppp-dsRNA), and profile the transcriptomes at three time points. Mapping expression quantitative trait loci (eQTL), we identify 417 response eQTLs (reQTLs) with varying effects between conditions. We characterize the dynamics of genetic regulation on early and late immune response and observe an enrichment of reQTLs in distal cis-regulatory elements. In addition, reQTLs are enriched for recent positive selection with an evolutionary trend towards enhanced immune response. Finally, we uncover reQTL effects in multiple GWAS loci and show a stronger enrichment for response than constant eQTLs in GWAS signals of several autoimmune diseases. This demonstrates the importance of infectious stimuli in modifying genetic predisposition to disease.Insight into the genetic influence on the immune response is important for the understanding of interindividual variability in human pathologies. Here, the authors generate transcriptome data from human blood monocytes stimulated with various immune stimuli and provide a time-resolved response eQTL map.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/28814792?dopt=Abstract</style></custom1></record></records></xml>