Genetic Regulation of Atherosclerosis-Relevant Phenotypes in Human Vascular Smooth Muscle Cells.
Animals
Aryl Hydrocarbon Receptor Nuclear Translocator
/ genetics
Atherosclerosis
/ genetics
Cell Movement
Cell Proliferation
Cells, Cultured
Disease Models, Animal
Female
Fibrosis
Genetic Predisposition to Disease
Genetic Variation
Genome-Wide Association Study
Humans
Male
Mice, Knockout, ApoE
Muscle, Smooth, Vascular
/ metabolism
Myocytes, Smooth Muscle
/ metabolism
Phenotype
Plaque, Atherosclerotic
Polymorphism, Single Nucleotide
cell proliferation
coronary artery disease
genome-wide association study
human genetics
Journal
Circulation research
ISSN: 1524-4571
Titre abrégé: Circ Res
Pays: United States
ID NLM: 0047103
Informations de publication
Date de publication:
04 12 2020
04 12 2020
Historique:
pubmed:
13
10
2020
medline:
25
5
2021
entrez:
12
10
2020
Statut:
ppublish
Résumé
Coronary artery disease (CAD) is a major cause of morbidity and mortality worldwide. Recent genome-wide association studies revealed 163 loci associated with CAD. However, the precise molecular mechanisms by which the majority of these loci increase CAD risk are not known. Vascular smooth muscle cells (VSMCs) are critical in the development of CAD. They can play either beneficial or detrimental roles in lesion pathogenesis, depending on the nature of their phenotypic changes. To identify genetic variants associated with atherosclerosis-relevant phenotypes in VSMCs. We quantified 12 atherosclerosis-relevant phenotypes related to calcification, proliferation, and migration in VSMCs isolated from 151 multiethnic heart transplant donors. After genotyping and imputation, we performed association mapping using 6.3 million genetic variants. We demonstrated significant variations in calcification, proliferation, and migration. These phenotypes were not correlated with each other. We performed genome-wide association studies for 12 atherosclerosis-relevant phenotypes and identified 4 genome-wide significant loci associated with at least one VSMC phenotype. We overlapped the previously identified CAD loci with our data set and found nominally significant associations at 79 loci. One of them was the chromosome 1q41 locus, which harbors Our data demonstrate that genetic variants have significant influences on VSMC function relevant to the development of atherosclerosis. Furthermore, high
Identifiants
pubmed: 33040646
doi: 10.1161/CIRCRESAHA.120.317415
pmc: PMC7718324
mid: NIHMS1637364
doi:
Substances chimiques
ARNT protein, human
0
TANGO protein, mouse
0
Aryl Hydrocarbon Receptor Nuclear Translocator
138391-32-9
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1552-1565Subventions
Organisme : NHLBI NIH HHS
ID : P01 HL030568
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL136314
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148239
Pays : United States
Organisme : NHLBI NIH HHS
ID : R21 HL135230
Pays : United States
Références
Nat Genet. 2017 Nov;49(11):1602-1612
pubmed: 28945252
J Cell Biol. 2011 May 30;193(5):935-51
pubmed: 21606205
Nat Genet. 2017 Jul;49(7):1113-1119
pubmed: 28530674
Science. 2016 Aug 19;353(6301):827-30
pubmed: 27540175
Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):E11349-E11358
pubmed: 30429326
Circulation. 2017 Aug 1;136(5):476-489
pubmed: 28487391
Bioinformatics. 2012 Jun 1;28(11):1530-2
pubmed: 22539670
Biochem Biophys Res Commun. 2017 Sep 16;491(2):396-402
pubmed: 28720499
Nature. 2012 Nov 1;491(7422):56-65
pubmed: 23128226
Arterioscler Thromb Vasc Biol. 2015 Oct;35(10):2207-17
pubmed: 26293461
Acta Physiol (Oxf). 2015 May;214(1):33-50
pubmed: 25677529
Biochim Biophys Acta Mol Basis Dis. 2017 Jun;1863(6):1640-1653
pubmed: 28341552
Cardiovasc Res. 2018 Jul 15;114(9):1241-1257
pubmed: 29617720
Circ Res. 2005 Feb 4;96(2):172-9
pubmed: 15625285
Hum Mol Genet. 2012 Sep 15;21(18):4021-9
pubmed: 22706276
Nat Med. 2016 Jun;22(6):657-65
pubmed: 27183216
J Cell Biol. 1988 Aug;107(2):771-80
pubmed: 3166463
Nat Genet. 2016 Oct;48(10):1284-1287
pubmed: 27571263
Nat Rev Genet. 2017 Jun;18(6):331-344
pubmed: 28286336
Atherosclerosis. 2019 Sep;288:175-185
pubmed: 31109707
Cell Tissue Res. 2012 Jan;347(1):155-75
pubmed: 21626289
Mol Med Rep. 2013 Aug;8(2):407-12
pubmed: 23784108
Cell. 2017 Jul 27;170(3):522-533.e15
pubmed: 28753427
J Clin Invest. 2012 Jan;122(1):70-9
pubmed: 22201681
Am J Hum Genet. 2013 Mar 7;92(3):366-74
pubmed: 23415669
Circ Res. 2016 Feb 19;118(4):692-702
pubmed: 26892967
Nat Genet. 2014 Feb;46(2):100-6
pubmed: 24473328
Cell Physiol Biochem. 2014;33(6):1827-37
pubmed: 24969327
Cytokine Growth Factor Rev. 2004 Aug;15(4):237-54
pubmed: 15207815
Arterioscler Thromb Vasc Biol. 2013 Jan;33(1):e1-e10
pubmed: 23162013
Nat Genet. 2013 Nov;45(11):1274-1283
pubmed: 24097068
Clin Immunol. 2010 Jan;134(1):33-46
pubmed: 19635683
Cell Rep. 2018 Oct 16;25(3):798-810.e6
pubmed: 30332657
Cell Signal. 2018 Dec;52:48-64
pubmed: 30172025
Nat Methods. 2011 Sep 04;8(10):833-5
pubmed: 21892150
Int J Med Sci. 2014 May 21;11(8):765-70
pubmed: 24936138
Am J Hum Genet. 2018 Sep 6;103(3):377-388
pubmed: 30146127
Nat Protoc. 2010 Sep;5(9):1564-73
pubmed: 21085122
Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2665-70
pubmed: 16477012
PLoS Genet. 2013;9(7):e1003652
pubmed: 23874238
Ann N Y Acad Sci. 1997 Apr 15;811:226-35; discussion 235-7
pubmed: 9186600
J Am Coll Cardiol. 2017 Feb 21;69(7):823-836
pubmed: 28209224
J Clin Invest. 1991 Dec;88(6):2039-46
pubmed: 1752961
Am J Nephrol. 2006;26(6):531-5
pubmed: 17159340
Bioinformatics. 2019 Jul 15;35(14):2495-2497
pubmed: 30520965
Nat Genet. 2018 Jul;50(7):956-967
pubmed: 29955180
Bioinformatics. 2011 Aug 1;27(15):2156-8
pubmed: 21653522
J Lipid Res. 2013 Jul;54(7):1894-905
pubmed: 23667179
PLoS Genet. 2015 May 28;11(5):e1005155
pubmed: 26020946
Cell. 2018 Dec 13;175(7):1796-1810.e20
pubmed: 30528432
PLoS Genet. 2011 Dec;7(12):e1002367
pubmed: 22144904
Am J Physiol. 1989 Dec;257(6 Pt 2):H1755-65
pubmed: 2690643
Circ Res. 2018 Feb 2;122(3):433-443
pubmed: 29212778
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Nucleic Acids Res. 2017 Jan 4;45(D1):D896-D901
pubmed: 27899670
Circ Genom Precis Med. 2018 Sep;11(9):e002115
pubmed: 30354329
Elife. 2015 Nov 14;4:
pubmed: 26568311
Circulation. 2018 Mar 20;137(12):e67-e492
pubmed: 29386200
Sci Rep. 2018 May 15;8(1):7595
pubmed: 29765072
Circ Res. 2016 Feb 19;118(4):564-78
pubmed: 26892958
PLoS Genet. 2014 Mar 27;10(3):e1004263
pubmed: 24676100
Am J Surg. 1995 Aug;170(2):193-7
pubmed: 7631929
Cell. 2009 Mar 6;136(5):891-902
pubmed: 19269366
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Am J Hum Genet. 2007 Sep;81(3):559-75
pubmed: 17701901
J Cell Physiol. 1990 Mar;142(3):635-42
pubmed: 2312620
Nat Rev Genet. 2014 Jan;15(1):34-48
pubmed: 24296534
Nat Genet. 2006 Aug;38(8):904-9
pubmed: 16862161
Bioinformatics. 2010 Sep 15;26(18):2336-7
pubmed: 20634204
Cardiovasc Res. 2012 Jul 15;95(2):156-64
pubmed: 22406749
Mol Biol Cell. 2011 Jul 1;22(13):2301-8
pubmed: 21525241
Nat Commun. 2016 Jul 08;7:12092
pubmed: 27386823
Lancet. 2017 Oct 21;390(10105):1833-1842
pubmed: 28855077
J Clin Invest. 2000 Oct;106(8):1011-20
pubmed: 11032861
Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H540-9
pubmed: 19525370
Cell. 2013 Jan 31;152(3):642-54
pubmed: 23333102
Nat Med. 2015 Jun;21(6):628-37
pubmed: 25985364