Lifelong reduction of LDL-cholesterol related to a common variant in the LDL-receptor gene decreases the risk of coronary artery disease--a Mendelian Randomisation study.

PloS One
Patrick Linsel-NitschkeCardiogenics Consortium

Abstract

Rare mutations of the low-density lipoprotein receptor gene (LDLR) cause familial hypercholesterolemia, which increases the risk for coronary artery disease (CAD). Less is known about the implications of common genetic variation in the LDLR gene regarding the variability of cholesterol levels and risk of CAD. Imputed genotype data at the LDLR locus on 1 644 individuals of a population-based sample were explored for association with LDL-C level. Replication of association with LDL-C level was sought for the most significant single nucleotide polymorphism (SNP) within the LDLR gene in three European samples comprising 6 642 adults and 533 children. Association of this SNP with CAD was examined in six case-control studies involving more than 15 000 individuals. Each copy of the minor T allele of SNP rs2228671 within LDLR (frequency 11%) was related to a decrease of LDL-C levels by 0.19 mmol/L (95% confidence interval (CI) [0.13-0.24] mmol/L, p = 1.5x10(-10)). This association with LDL-C was uniformly found in children, men, and women of all samples studied. In parallel, the T allele of rs2228671 was associated with a significantly lower risk of CAD (Odds Ratio per copy of the T allele: 0.82, 95% CI [0.76-0.89], p = 2.1x10(-7)). Ad...Continue Reading

References

May 29, 1998·Circulation·P W WilsonW B Kannel
May 29, 1998·The New England Journal of Medicine·A Tybjaerg-HansenB G Nordestgaard
Apr 9, 1999·International Journal of Epidemiology·M BlettnerC Friedenreich
Apr 12, 2003·International Journal of Epidemiology·George Davey Smith, Shah Ebrahim
Apr 13, 2004·International Journal of Epidemiology·Duncan C Thomas, David V Conti
Apr 13, 2004·International Journal of Epidemiology·George Davey Smith, Shah Ebrahim
Mar 10, 2005·The New England Journal of Medicine·John C LaRosaUNKNOWN Treating to New Targets (TNT) Investigators
Jul 21, 2005·Das Gesundheitswesen·H-E WichmannUNKNOWN MONICA/KORA Study Group
Aug 24, 2005·International Journal of Epidemiology·Cosetta MinelliJohn Attia
Mar 24, 2006·The New England Journal of Medicine·Jonathan C CohenHelen H Hobbs
Mar 25, 2006·Science·Michael S Brown, Joseph L Goldstein
Apr 20, 2006·Annals of Epidemiology·Leonelo E BautistaJuan P Casas
May 23, 2007·The Journal of Pediatrics·Thomas ReinehrWerner Andler
Jul 4, 2007·Statistical Applications in Genetics and Molecular Biology·Pantelis G Bagos, Georgios K Nikolopoulos
Jul 20, 2007·The New England Journal of Medicine·Nilesh J SamaniUNKNOWN WTCCC and the Cardiogenics Consortium
Sep 22, 2007·Statistics in Medicine·Debbie A LawlorGeorge Davey Smith
Oct 19, 2007·Nature·UNKNOWN International HapMap ConsortiumJohn Stewart
Nov 27, 2007·International Journal of Epidemiology·Cosetta MinelliJohn Attia
Dec 19, 2007·Circulation·Wolfgang LiebJeanette Erdmann
Dec 28, 2007·The Journal of Clinical Endocrinology and Metabolism·Marianne BennAnne Tybjaerg-Hansen
Jan 9, 2008·American Journal of Human Genetics·Chris WallacePatricia B Munroe
Jan 15, 2008·Nature Genetics·Cristen J WillerGonçalo R Abecasis
Feb 12, 2008·Lancet·Manjinder S SandhuVincent Mooser
Mar 21, 2008·The New England Journal of Medicine·Sekar KathiresanMarju Orho-Melander
Aug 30, 2008·Circulation·Hendrik BonnemeierHeribert Schunkert

❮ Previous
Next ❯

Citations

Aug 14, 2009·Nutrition Reviews·Lu Qi
Jul 9, 2010·Future Cardiology·Christopher T JohansenRobert A Hegele
Dec 3, 2013·Current Atherosclerosis Reports·Jaideep PatelH Robert Superko
Nov 6, 2009·European Journal of Epidemiology·Gabriella AndreottiAnn W Hsing
Nov 7, 2009·BMJ : British Medical Journal·Hannah KuperHarry Hemingway
Jul 10, 2010·International Journal of Environmental Research and Public Health·Murielle Bochud, Valentin Rousson
Jan 17, 2012·American Journal of Epidemiology·M Maria GlymourJames M Robins
Feb 10, 2009·Nature Genetics·UNKNOWN Myocardial Infarction Genetics ConsortiumDavid Altshuler
Sep 23, 2008·Molecular Diagnosis & Therapy·Heribert SchunkertJeanette Erdmann
May 12, 2012·British Medical Bulletin·Daniel I SwerdlowSteve E Humphries
Apr 6, 2013·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·E C OelsnerR G Barr
Dec 17, 2014·Circulation Journal : Official Journal of the Japanese Circulation Society·Sang Eun Lee, Hyo-Soo Kim
Feb 26, 2016·Current Opinion in Endocrinology, Diabetes, and Obesity·Stephen Burgess, Eric Harshfield
Sep 19, 2015·Current Opinion in Lipidology·Simone L VerweijErik S G Stroes
May 9, 2015·International Journal of Epidemiology·Anna G C BoefSaskia le Cessie
May 29, 2015·Nature Communications·Omar S AhmadJ Brent Richards
Jul 5, 2016·The British Journal of Nutrition·Nadia MansoorKjetil Retterstøl
Jun 28, 2016·International Journal of Epidemiology·Daniel I SwerdlowAroon D Hingorani
Nov 2, 2016·Journal of the American Society of Nephrology : JASN·Peggy SekulaAnna Köttgen
Dec 2, 2011·The New England Journal of Medicine·Christopher J O'Donnell, Elizabeth G Nabel
Mar 12, 2015·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Gerlinde A S MetzDavid M Olson
Mar 16, 2017·Journal of Internal Medicine·A G OlssonL Yvan-Charvet
May 10, 2017·American Journal of Respiratory and Critical Care Medicine·John P ReillyNuala J Meyer
Nov 29, 2017·Scientific Reports·Catherine IgartuaCarole Ober
Jun 30, 2018·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Stephen T VernonGemma A Figtree
Apr 24, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Lara M MangraviteRonald M Krauss
Aug 30, 2014·Circulation. Cardiovascular Genetics·Hayato TadaSekar Kathiresan

❮ Previous
Next ❯

Methods Mentioned

BETA
genotyping

Software Mentioned

polychor
SEPATH
MPlus
R

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.