MARC details
| 000 -LEADER |
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| fixed length control field |
04838nam a22005417a 4500 |
| 008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION |
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| fixed length control field |
160113s20152015 xxu||||| |||| 00| 0 eng d |
| 022 ## - INTERNATIONAL STANDARD SERIAL NUMBER |
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| International Standard Serial Number |
0028-0836 |
| 040 ## - CATALOGING SOURCE |
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| Original cataloging agency |
Ovid MEDLINE(R) |
| 099 ## - LOCAL FREE-TEXT CALL NUMBER (OCLC) |
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| PMID |
25487149 |
| 245 ## - TITLE STATEMENT |
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| Title |
Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. |
| 251 ## - Source |
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| Source |
Nature. 518(7537):102-6, 2015 Feb 5. |
| 252 ## - Abbreviated Source |
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| Abbreviated source |
Nature. 518(7537):102-6, 2015 Feb 5. |
| 253 ## - Journal Name |
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| Journal name |
Nature |
| 266 ## - Date added to catalog |
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| Date added to catalog |
2016-01-13 |
| 501 ## - WITH NOTE |
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| Local holdings |
Available online from MWHC library: 1995 - 2009, Available in print through MWHC library: 1999 - 2006 |
| 520 ## - SUMMARY, ETC. |
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| Abstract |
Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance. When MI occurs early in life, genetic inheritance is a major component to risk. Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to MI risk in individual families, whereas common variants at more than 45 loci have been associated with MI risk in the population. Here we evaluate how rare mutations contribute to early-onset MI risk in the population. We sequenced the protein-coding regions of 9,793 genomes from patients with MI at an early age (<50 years in males and <60 years in females) along with MI-free controls. We identified two genes in which rare coding-sequence mutations were more frequent in MI cases versus controls at exome-wide significance. At low-density lipoprotein receptor (LDLR), carriers of rare non-synonymous mutations were at 4.2-fold increased risk for MI; carriers of null alleles at LDLR were at even higher risk (13-fold difference). Approximately 2% of early MI cases harbour a rare, damaging mutation in LDLR; this estimate is similar to one made more than 40 years ago using an analysis of total cholesterol. Among controls, about 1 in 217 carried an LDLR coding-sequence mutation and had plasma LDL cholesterol > 190 mg dl(-1). At apolipoprotein A-V (APOA5), carriers of rare non-synonymous mutations were at 2.2-fold increased risk for MI. When compared with non-carriers, LDLR mutation carriers had higher plasma LDL cholesterol, whereas APOA5 mutation carriers had higher plasma triglycerides. Recent evidence has connected MI risk with coding-sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase and apolipoprotein C-III (refs 18, 19). Combined, these observations suggest that, as well as LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk. |
| 546 ## - LANGUAGE NOTE |
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| Language note |
English |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
*Alleles |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
*Apolipoproteins A/ge [Genetics] |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
*Exome/ge [Genetics] |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
*Genetic Predisposition to Disease/ge [Genetics] |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
*Myocardial Infarction/ge [Genetics] |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
*Receptors, LDL/ge [Genetics] |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
Age Factors |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
Age of Onset |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
Case-Control Studies |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
Cholesterol, LDL/bl [Blood] |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
Coronary Artery Disease/ge [Genetics] |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
Female |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
Genetics, Population |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
Heterozygote |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
Humans |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
Male |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
Middle Aged |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
Mutation/ge [Genetics] |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
Myocardial Infarction/bl [Blood] |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
National Heart, Lung, and Blood Institute (U.S.) |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
Triglycerides/bl [Blood] |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
United States |
| 651 ## - SUBJECT ADDED ENTRY--GEOGRAPHIC NAME |
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| Institution |
MedStar Health Research Institute |
| 657 ## - INDEX TERM--FUNCTION |
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| Medline publication type |
Journal Article |
| 657 ## - INDEX TERM--FUNCTION |
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| Medline publication type |
Research Support, N.I.H., Extramural |
| 657 ## - INDEX TERM--FUNCTION |
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| Medline publication type |
Research Support, Non-U.S. Gov't |
| 700 ## - ADDED ENTRY--PERSONAL NAME |
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| Local Authors |
Epstein, Stephen E |
| 790 ## - Authors |
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| All authors |
Abecasis GR, Allayee H, Altshuler D, Angelica Merlini P, Ardissino D, Asselta R, Assimes TL, Auer PL, Bamshad MJ, Boerwinkle E, Burke GL, Carlson CS, Clarke R, Cresci S, Cupples LA, Danesh J, Davies R, DePristo MA, Do R, Donnelly P, Duga S, Epstein SE, Erdmann J, Farlow DN, Farrall M, Folsom AR, Gabriel S, Girelli D, Goel A, Gross M, Guella I, Hamsten A, Hartiala J, Hazen SL, Hechter E, Hegele RA, Heiss G, Herrington DM, Hovingh GK, Huang J, Jackson RD, Johansen CT, Johnson AD, Jorgensen AB, Kastelein JJ, Kathiresan S, Kiezun A, Kleber ME, Kooperberg C, Kraus WE, Lander ES, Lange EM, Lange LA, Li M, Liu Y, Martinelli N, Marz W, McPherson R, NHLBI Exome Sequencing Project, Nickerson DA, Nikpay M, O'Donnell CJ, Olivieri O, Peloso GM, Psaty BM, Rader DJ, Reilly DF, Reilly MP, Reiner AP, Rich SS, Rivas MA, Roberts R, Rossouw JE, Saleheen D, Samani NJ, Schunkert H, Schwartz SM, Shah SH, Siscovick DS, Sivapalaratnam S, Spertus JA, Stewart AF, Stitziel NO, Sunyaev SR, Tang WH, Taylor HA, Tracy RP, Tybjaerg-Hansen A, Wang J, Watkins H, Wilson JG, Won HH, Yin W, Zuk O |
| 856 ## - ELECTRONIC LOCATION AND ACCESS |
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| DOI |
<a href="http://dx.doi.org/10.1038/nature13917">http://dx.doi.org/10.1038/nature13917</a> |
| Public note |
http://dx.doi.org/10.1038/nature13917 |
| 942 ## - ADDED ENTRY ELEMENTS (KOHA) |
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| Koha item type |
Journal Article |
| Item type description |
Journal article |
