Evidence map›Paper›PMID 24867879›Full record

ArticleCirculation. Cardiovascular genetics2014

A novel molecular diagnostic marker for familial and early-onset coronary artery disease and myocardial infarction in the LRP8 gene.

Gong-Qing Shen, Domenico Girelli, Lin Li, Shaoqi Rao, Stephen Archacki, Oliviero Olivieri, Nicola Martinelli, Jeong Euy Park, Qiuyun Chen, Eric J Topol and 1 more

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Article in Circulation. Cardiovascular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

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19citing papers in PubMed, 1 pooled it
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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  5. Tale of 2 Receptors.Arteriosclerosis, thrombosis, and vascular biology · 2025
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  6. Review
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  11. Angiotensin II Infusion Leads to Aortic Dissection in LRP8 Deficient Mice.International journal of molecular sciences · 2020
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  12. Review
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  14. Article
  15. New Insights in the Pathophysiology of Antiphospholipid Syndrome.Seminars in thrombosis and hemostasis · 2018
    Review
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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Gong-Qing ShenFrom the Department of Molecular Cardiology, Center for Cardiovascular Genetics, Lerner Research Institute, Cleveland Clinic, OH (G.-Q.S., L.L., S.R., S.A., Q.C., Q.K.W.); Department of Medicine, University of Verona, Verona, Italy (D.G., O.O., N.M.); Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea (J.E.P.); The Scripps Research Institute, Scripps Clinic, La Jolla, CA (E.J.T.); and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China (Q.K.W.).
Domenico GirelliFrom the Department of Molecular Cardiology, Center for Cardiovascular Genetics, Lerner Research Institute, Cleveland Clinic, OH (G.-Q.S., L.L., S.R., S.A., Q.C., Q.K.W.); Department of Medicine, University of Verona, Verona, Italy (D.G., O.O., N.M.); Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea (J.E.P.); The Scripps Research Institute, Scripps Clinic, La Jolla, CA (E.J.T.); and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China (Q.K.W.).
Lin LiFrom the Department of Molecular Cardiology, Center for Cardiovascular Genetics, Lerner Research Institute, Cleveland Clinic, OH (G.-Q.S., L.L., S.R., S.A., Q.C., Q.K.W.); Department of Medicine, University of Verona, Verona, Italy (D.G., O.O., N.M.); Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea (J.E.P.); The Scripps Research Institute, Scripps Clinic, La Jolla, CA (E.J.T.); and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China (Q.K.W.).
Shaoqi RaoFrom the Department of Molecular Cardiology, Center for Cardiovascular Genetics, Lerner Research Institute, Cleveland Clinic, OH (G.-Q.S., L.L., S.R., S.A., Q.C., Q.K.W.); Department of Medicine, University of Verona, Verona, Italy (D.G., O.O., N.M.); Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea (J.E.P.); The Scripps Research Institute, Scripps Clinic, La Jolla, CA (E.J.T.); and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China (Q.K.W.).
Stephen ArchackiFrom the Department of Molecular Cardiology, Center for Cardiovascular Genetics, Lerner Research Institute, Cleveland Clinic, OH (G.-Q.S., L.L., S.R., S.A., Q.C., Q.K.W.); Department of Medicine, University of Verona, Verona, Italy (D.G., O.O., N.M.); Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea (J.E.P.); The Scripps Research Institute, Scripps Clinic, La Jolla, CA (E.J.T.); and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China (Q.K.W.).
Oliviero OlivieriFrom the Department of Molecular Cardiology, Center for Cardiovascular Genetics, Lerner Research Institute, Cleveland Clinic, OH (G.-Q.S., L.L., S.R., S.A., Q.C., Q.K.W.); Department of Medicine, University of Verona, Verona, Italy (D.G., O.O., N.M.); Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea (J.E.P.); The Scripps Research Institute, Scripps Clinic, La Jolla, CA (E.J.T.); and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China (Q.K.W.).
Nicola MartinelliFrom the Department of Molecular Cardiology, Center for Cardiovascular Genetics, Lerner Research Institute, Cleveland Clinic, OH (G.-Q.S., L.L., S.R., S.A., Q.C., Q.K.W.); Department of Medicine, University of Verona, Verona, Italy (D.G., O.O., N.M.); Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea (J.E.P.); The Scripps Research Institute, Scripps Clinic, La Jolla, CA (E.J.T.); and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China (Q.K.W.).
Jeong Euy ParkFrom the Department of Molecular Cardiology, Center for Cardiovascular Genetics, Lerner Research Institute, Cleveland Clinic, OH (G.-Q.S., L.L., S.R., S.A., Q.C., Q.K.W.); Department of Medicine, University of Verona, Verona, Italy (D.G., O.O., N.M.); Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea (J.E.P.); The Scripps Research Institute, Scripps Clinic, La Jolla, CA (E.J.T.); and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China (Q.K.W.).
Qiuyun ChenFrom the Department of Molecular Cardiology, Center for Cardiovascular Genetics, Lerner Research Institute, Cleveland Clinic, OH (G.-Q.S., L.L., S.R., S.A., Q.C., Q.K.W.); Department of Medicine, University of Verona, Verona, Italy (D.G., O.O., N.M.); Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea (J.E.P.); The Scripps Research Institute, Scripps Clinic, La Jolla, CA (E.J.T.); and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China (Q.K.W.).
Eric J TopolFrom the Department of Molecular Cardiology, Center for Cardiovascular Genetics, Lerner Research Institute, Cleveland Clinic, OH (G.-Q.S., L.L., S.R., S.A., Q.C., Q.K.W.); Department of Medicine, University of Verona, Verona, Italy (D.G., O.O., N.M.); Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea (J.E.P.); The Scripps Research Institute, Scripps Clinic, La Jolla, CA (E.J.T.); and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China (Q.K.W.).
Qing K WangFrom the Department of Molecular Cardiology, Center for Cardiovascular Genetics, Lerner Research Institute, Cleveland Clinic, OH (G.-Q.S., L.L., S.R., S.A., Q.C., Q.K.W.); Department of Medicine, University of Verona, Verona, Italy (D.G., O.O., N.M.); Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea (J.E.P.); The Scripps Research Institute, Scripps Clinic, La Jolla, CA (E.J.T.); and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China (Q.K.W.). wangq2@ccf.org qkwang@mail.hust.edu.cn.

Funding

NGS in Large CAD Families: In-Depth Identification of Rare Risk Genomic VariantsR01HL121358 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI WANG, QING KENNETH · 2014 to 2017
$2.8M
Novel Role of a Nucleoporin Gene in Atrial Fibrillation, the Most Common CardiacR01HL094498 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI WANG, QING KENNETH · 2010 to 2013
$1.5M
NHLBI NIH HHS R01 HL094498NHLBI NIH HHS R01 HL121358
6 · The paper itself

Abstract

backgroundMany single-nucleotide polymorphisms have been associated with coronary artery disease (CAD)/myocardial infarction (MI) by genome-wide association studies, but the diagnostic value of these variants is limited. Functional single-nucleotide polymorphism R952Q in LRP8 is associated with familial and early-onset CAD/MI. The objective of this study is to test whether fine mapping and haplotype analysis for single-nucleotide polymorphisms flanking R952Q may identify a haplotype that may serve as a molecular diagnostic marker for familial and early-onset CAD/MI. METHODS AND

resultsFive single-nucleotide polymorphisms (rs7546246, rs2297660, rs3737983, R952Q, and rs5177) were genotyped and analyzed in GeneQuest (381 patients with familial, early-onset CAD and 183 patients with MI versus 560 controls) and the Italian population (248 patients with familial MI versus 308 controls). One novel risk haplotype, TACGC, was found only in patients with CAD and MI but not in controls. It was significantly associated with CAD (P=7.4×10(-7)) and MI (P=2.2×10(-9)) in GeneQuest. The finding was replicated in the Italian cohort (P=0.041). Sib-transmission disequilibrium test analysis showed a significant association between haplotype TACGC and CAD in GeneQuest II (P=0.039). Haplotype TACGC was not present in a South Korean population of 611 patients with CAD and 294 normal controls. TACGC/TACGC homozygotes tended to develop CAD/MI earlier and showed higher low-density lipoprotein cholesterol levels than heterozygotes (P<0.05).

conclusionsThe rare haplotype TACGC in LRP8 confers a significant risk of familial, early-onset CAD/MI. Because the risk haplotype exists only in patients with familial and early-onset CAD/MI, we propose that it may be a molecular diagnostic marker for diagnosis of familial, early-onset CAD/MI in some white populations.

Indexed as

AdultAgedAge of OnsetAsian PeopleBase SequenceCase-Control StudiesCholesterol, LDLCohort StudiesCoronary Artery DiseaseFemaleGenotypeHaplotypesHomozygoteHumansItalyLDL-Receptor Related ProteinsCholesterol, LDLLDL-Receptor Related Proteinslow density lipoprotein receptor-related protein 8cardiovascular diseasesmyocardial infarctionpolymorphism, single nucleotide

Identifiers

PMID24867879
PMCPMC4140990

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