Calcium Signaling Pathway Genes RUNX2 and CACNA1C Are Associated with Calcific Aortic Valve Disease

Circulation: Cardiovascular Genetics

Volumn 8, Issue 6, 2015, Pages 812-822

  Guauque Olarte, Sandra ^a   Messika Zeitoun, David ^c,d   Droit, Arnaud ^b,e   Lamontagne, Maxime ^a   Tremblay Marchand, Joel ^a   Lavoie Charland, Emilie ^a   Gaudreault, Nathalie ^a   Arsenault, Benoit J ^g   Dube, Marie Pierre ^b,f   Tardif, Jean Claude ^f   Body, Simon C ^h   Seidman, Jonathan G ⁱ   Boileau, Catherine ^c   Mathieu, Patrick ^a   Pibarot, Philippe ^a,b   Bosse, Yohan ^a,b  

^a LAVAL UNIVERSITY   (Canada)

^b UNIVERSITÉ LAVAL   (Canada)

^c BICHAT HOSPITAL   (France)

^d INSERM   (France)

^e University Laval   (Canada)

^f MONTREAL HEART INSTITUTE   (Canada)

^g UNIVERSITÉ DE MONTRÉAL   (Canada)

^h BRIGHAM AND WOMEN S HOSPITAL   (United States)

ⁱ HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Aortic valve calcification; aortic valve stenosis; eQTL; gene expression; genome wide association study; genomics; RNA Seq

Indexed keywords

CALCIUM; MESSENGER RNA; TRANSCRIPTION FACTOR RUNX2; CACNA1C PROTEIN, HUMAN; CALCIUM CHANNEL L TYPE; RUNX2 PROTEIN, HUMAN;

AORTA VALVE STENOSIS; ARTICLE; CACNA1C GENE; CALCIUM SIGNALING; CONTROLLED STUDY; FRANCE; GENE; GENE EXPRESSION; GENETIC ASSOCIATION; GENETIC SUSCEPTIBILITY; GENOTYPE; HUMAN; HUMAN TISSUE; MAJOR CLINICAL STUDY; PHENOTYPE; PRIORITY JOURNAL; QUANTITATIVE TRAIT LOCUS; RNA SEQUENCE; RUNX2 GENE; SINGLE NUCLEOTIDE POLYMORPHISM; UPREGULATION; AORTA VALVE; CALCINOSIS; CASE CONTROL STUDY; CLINICAL TRIAL; FEMALE; GENETIC DATABASE; GENETICS; GENOME-WIDE ASSOCIATION STUDY; MALE; METABOLISM; MULTICENTER STUDY; PATHOLOGY;

AORTIC VALVE; AORTIC VALVE STENOSIS; CALCINOSIS; CALCIUM CHANNELS, L-TYPE; CALCIUM SIGNALING; CASE-CONTROL STUDIES; CORE BINDING FACTOR ALPHA 1 SUBUNIT; DATABASES, GENETIC; FEMALE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; MALE; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 84950144426     PISSN: 1942325X     EISSN: 19423268     Source Type: Journal    
DOI: 10.1161/CIRCGENETICS.115.001145     Document Type: Article

References (45)

1. Carabello BA, Paulus WJ. Aortic stenosis. Lancet. 2009;373:956-966. doi: 10.1016/S0140-6736(09)60211-7.
2. Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of valvular heart diseases: a population-based study. Lancet. 2006;368:1005-1011. doi: 10.1016/S0140-6736(06)69208-8.
3. Otto CM, Burwash IG, Legget ME, Munt BI, Fujioka M, Healy NL, et al. Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome. Circulation. 1997;95:2262-2270.
4. Cowell SJ, Newby DE, Prescott RJ, Bloomfield P, Reid J, Northridge DB, et al.; Scottish Aortic Stenosis and Lipid Lowering Trial, Impact on Regression (SALTIRE) Investigators. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. N Engl J Med. 2005;352:2389-2397. doi: 10.1056/NEJMoa043876.
5. Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, et al.; SEAS Investigators. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008;359:1343-1356. doi: 10.1056/NEJMoa0804602.
6. Rajamannan NM, Bonow RO, Rahimtoola SH. Calcific aortic stenosis: an update. Nat Clin Pract Cardiovasc Med. 2007;4:254-262. doi: 10.1038/ncpcardio0827.
7. Sehatzadeh S, Doble B, Xie F, Blackhouse G, Campbell K, Kaulback K, et al. Transcatheter aortic valve implantation (TAVI) for treatment of aortic valve stenosis: an evidence update. Ont Health Technol Assess Ser. 2013;13:1-40.
8. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al.; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2015 update: a report from the American Heart Association. Circulation. 2015;131:e29-322. doi: 10.1161/CIR.0000000000000152.
9. Bossé Y, Miqdad A, Fournier D, Pépin A, Pibarot P, Mathieu P. Refining molecular pathways leading to calcific aortic valve stenosis by studying gene expression profile of normal and calcified stenotic human aortic valves. Circ Cardiovasc Genet. 2009;2:489-498. doi: 10.1161/CIRCGENETICS.108.820795.
10. Horne BD, Camp NJ, Muhlestein JB, Cannon-Albright LA. Evidence for a heritable component in death resulting from aortic and mitral valve diseases. Circulation. 2004;110:3143-3148. doi: 10.1161/01. CIR.0000147189.85636.C3.
11. Probst V, Le Scouarnec S, Legendre A, Jousseaume V, Jaafar P, Nguyen JM, et al. Familial aggregation of calcific aortic valve stenosis in the western part of France. Circulation. 2006;113:856-860. doi: 10.1161/CIRCULATIONAHA.105.569467.
12. Gaudreault N, Ducharme V, Lamontagne M, Guauque-Olarte S, Mathieu P, Pibarot P, et al. Replication of genetic association studies in aortic stenosis in adults. Am J Cardiol. 2011;108:1305-1310. doi: 10.1016/j.amjcard.2011.06.050.
13. Ducharme V, Guauque-Olarte S, Gaudreault N, Pibarot P, Mathieu P, Bossé Y. NOTCH1 genetic variants in patients with tricuspid calcific aortic valve stenosis. J Heart Valve Dis. 2013;22:142-149.
14. Garg V, Muth AN, Ransom JF, Schluterman MK, Barnes R, King IN, et al. Mutations in NOTCH1 cause aortic valve disease. Nature. 2005;437:270-274. doi: 10.1038/nature03940.
15. Thanassoulis G, Campbell CY, Owens DS, Smith JG, Smith AV, Peloso GM, et al.; CHARGE Extracoronary Calcium Working Group. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med. 2013;368:503-512. doi: 10.1056/NEJMoa1109034.
16. Mailman MD, Feolo M, Jin Y, Kimura M, Tryka K, Bagoutdinov R, et al. The NCBI dbGaP database of genotypes and phenotypes. Nat Genet. 2007;39:1181-1186. doi: 10.1038/ng1007-1181.
17. Delaneau O, Marchini J, Zagury JF. A linear complexity phasing method for thousands of genomes. Nat Methods. 2012;9:179-181. doi: 10.1038/nmeth.1785.
18. Howie BN, Donnelly P, Marchini J. A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet. 2009;5:e1000529. doi: 10.1371/journal.pgen.1000529.
19. Patterson N, Price AL, Reich D. Population structure and eigenanalysis. PLoS Genet. 2006;2:e190. doi: 10.1371/journal.pgen.0020190.
20. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81:559-575. doi: 10.1086/519795.
21. Pruim RJ, Welch RP, Sanna S, Teslovich TM, Chines PS, Gliedt TP, et al. LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics. 2010;26:2336-2337. doi: 10.1093/bioinformatics/btq419.
22. Nam D, Kim J, Kim SY, Kim S. GSA-SNP: a general approach for gene set analysis of polymorphisms. Nucleic Acids Res. 2010;38(Web Server issue):W749-W754. doi: 10.1093/nar/gkq428.
23. Yu W, Clyne M, Khoury MJ, Gwinn M. Phenopedia and Genopedia: disease-centered and gene-centered views of the evolving knowledge of human genetic associations. Bioinformatics. 2010;26:145-146. doi: 10.1093/bioinformatics/btp618.
24. Warren BA, Yong JL. Calcification of the aortic valve: its progression and grading. Pathology. 1997;29:360-368.
25. Trapnell C, Hendrickson DG, Sauvageau M, Goff L, Rinn JL, Pachter L. Differential analysis of gene regulation at transcript resolution with RNAseq. Nat Biotechnol. 2013;31:46-53. doi: 10.1038/nbt.2450.
26. Anders S, Huber W. Differential expression analysis for sequence count data. Genome Biol. 2010;11:R106. doi: 10.1186/gb-2010-11-10-r106.
27. Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26:139-140. doi: 10.1093/bioinformatics/btp616.
28. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 2004;5:R80. doi: 10.1186/gb-2004-5-10-r80.
29. Du P, Kibbe WA, Lin SM. lumi: a pipeline for processing Illumina microarray. Bioinformatics. 2008;24:1547-1548. doi: 10.1093/bioinformatics/btn224.
30. Nordström P, Glader CA, Dahlén G, Birgander LS, Lorentzon R, Waldenström A, et al. Oestrogen receptor alpha gene polymorphism is related to aortic valve sclerosis in postmenopausal women. J Intern Med. 2003;254:140-146.
31. Panagiotou OA, Ioannidis JP; Genome-Wide Significance Project. What should the genome-wide significance threshold be Empirical replication of borderline genetic associations. Int J Epidemiol. 2012;41:273-286. doi: 10.1093/ije/dyr178.
32. Manolio TA. Bringing genome-wide association findings into clinical use. Nat Rev Genet. 2013;14:549-558. doi: 10.1038/nrg3523.
33. Hennessey JA, Boczek NJ, Jiang YH, Miller JD, Patrick W, Pfeiffer R, et al. A CACNA1C variant associated with reduced voltage-dependent inactivation, increased CaV1.2 channel window current, and arrhythmogenesis. PLoS One. 2014;9:e106982. doi: 10.1371/journal.pone.0106982.
34. Johnson AD, Newton-Cheh C, Chasman DI, Ehret GB, Johnson T, Rose L, et al.; Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium; Global BPgen Consortium; Womens Genome Health Study. Association of hypertension drug target genes with blood pressure and hypertension in 86,588 individuals. Hypertension. 2011;57:903-910. doi: 10.1161/HYPERTENSIONAHA.110.158667.
35. Wang W, Pang L, Palade P. Angiotensin II upregulates Ca(V)1.2 protein expression in cultured arteries via endothelial H(2)O(2) production. J Vasc Res. 2011;48:67-78. doi: 10.1159/000318776.
36. Helske S, Lindstedt KA, Laine M, Maÿränpaä M, Werkkala K, Lommi J, et al. Induction of local angiotensin II-producing systems in stenotic aortic valves. J Am Coll Cardiol. 2004;44:1859-1866. doi: 10.1016/j.jacc.2004.07.054.
37. OBrien KD, Shavelle DM, Caulfield MT, McDonald TO, Olin-Lewis K, Otto CM, et al. Association of angiotensin-converting enzyme with lowdensity lipoprotein in aortic valvular lesions and in human plasma. Circulation. 2002;106:2224-2230.
38. El Husseini D, Boulanger MC, Mahmut A, Bouchareb R, Laflamme MH, Fournier D, et al. P2Y2 receptor represses IL-6 expression by valve interstitial cells through Akt: implication for calcific aortic valve disease. J Mol Cell Cardiol. 2014;72:146-156. doi: 10.1016/j.yjmcc.2014.02.014.
39. Le Quang K, Bouchareb R, Lachance D, Laplante MA, El Husseini D, Boulanger MC, et al. Early development of calcific aortic valve disease and left ventricular hypertrophy in a mouse model of combined dyslipidemia and type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol. 2014;34:2283-2291. doi: 10.1161/ATVBAHA.114.304205.
40. Towler DA. Molecular and cellular aspects of calcific aortic valve disease. Circ Res. 2013;113:198-208. doi: 10.1161/CIRCRESAHA.113.300155.
41. Nagy E, Eriksson P, Yousry M, Caidahl K, Ingelsson E, Hansson GK, et al. Valvular osteoclasts in calcification and aortic valve stenosis severity. Int J Cardiol. 2013;168:2264-2271. doi: 10.1016/j.ijcard.2013.01.207.
42. Arsenault BJ, Boekholdt SM, Dubé MP, Rheaúme E, Wareham NJ, Khaw KT, et al. Lipoprotein(a) levels, genotype, and incident aortic valve stenosis: a prospective Mendelian randomization study and replication in a case-control cohort. Circ Cardiovasc Genet. 2014;7:304-310. doi: 10.1161/CIRCGENETICS.113.000400.
43. Colhoun HM, McKeigue PM, Davey Smith G. Problems of reporting genetic associations with complex outcomes. Lancet. 2003;361:865-872.
44. Dimas AS, Deutsch S, Stranger BE, Montgomery SB, Borel C, Attar-Cohen H, et al. Common regulatory variation impacts gene expression in a cell type-dependent manner. Science. 2009;325:1246-1250. doi: 10.1126/science.1174148.
45. Fu J, Wolfs MG, Deelen P, Westra HJ, Fehrmann RS, Te Meerman GJ, et al. Unraveling the regulatory mechanisms underlying tissue-dependent genetic variation of gene expression. PLoS Genet. 2012;8:e1002431. doi: 10.1371/journal.pgen.1002431.