NOS1AP is a genetic modifier of the long-QT syndrome

Circulation

Volumn 120, Issue 17, 2009, Pages 1657-1663

  George, Alfred L ⁱ   Crotti, Lia ^a,c,d   Monti, Maria Cristina ^b,e   Insolia, Roberto ^d   Peljto, Anna ^c   Goosen, Althea ^f   Brink, Paul A ^f   Greenberg, David A ^e   Schwartz, Peter J ^a,c,d,f,g,h  

^a Section of Cardiology   (United States)

^b UNIVERSITY OF PAVIA   (Italy)

^c Department of Cardiology ^*

^d FONDAZIONE IRCCS POLICLINICO SAN MATTEO   (Italy)

^e Mailman School of Public Health ^*  (United States)

^f STELLENBOSCH UNIVERSITY   (South Africa)

^g ISTITUTO AUXOLOGICO ITALIANO   (Italy)

^h UNIVERSITY OF CAPE TOWN   (South Africa)

ⁱ Institute for Integrative Genomics   (United States)

Author keywords

Arrhythmia; Genetics; KCNQ1 protein, human; Long QT syndrome; Nitric oxide synthase

Indexed keywords

NEURONAL NITRIC OXIDE SYNTHASE; POTASSIUM CHANNEL KCNQ1; PROTEIN NOS1AP; UNCLASSIFIED DRUG;

ARTICLE; CHILD; CONTROLLED STUDY; DISEASE SEVERITY; FEMALE; GENE FREQUENCY; GENE MUTATION; GENETIC ASSOCIATION; GENETIC RISK; GENETIC VARIABILITY; HEART ARREST; HETEROZYGOTE; HUMAN; LONG QT SYNDROME; MAJOR CLINICAL STUDY; MALE; MUTATIONAL ANALYSIS; PRESCHOOL CHILD; PRIORITY JOURNAL; QT INTERVAL; SCHOOL CHILD; SOUTH AFRICA; SUDDEN DEATH;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ARRHYTHMIAS, CARDIAC; DEATH, SUDDEN; FEMALE; GENETIC MARKERS; GENETIC VARIATION; HUMANS; LONG QT SYNDROME; MALE; MUTATION; RISK FACTORS;

EID: 70350540922     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.109.879643     Document Type: Article

References (33)

1. Schwartz PJ, Crotti L. Long QT and short QT syndrome. In: Zipes DP, Jalife J, eds. Cardiac Electrophysiology: From Cell to Bedside. 5th ed. Philadelphia, Pa: Elsevier/Saunders; 2009:731-744
2. Wang Q, Curran ME, Splawski I, Burn TC, Millholland JM, VanRaay TJ, Shen J, Timothy KW, Vincent GM, de Jager T, Schwartz PJ, Towbin JA, Moss AJ, Atkinson DL, Landes GM, Connors TD, Keating MT. Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet. 1996;12:17-23
3. Priori SG, Napolitano C, Schwartz PJ. Low penetrance in the long-QT syndrome: clinical impact. Circulation. 1999;99:529-533
4. Schwartz PJ, Priori SG, Napolitano C. How really rare are rare diseases? The intriguing case of independent compound mutations in the long QT syndrome. J Cardiovasc Electrophysiol. 2003;14:1120-1121
5. Crotti L, Lundquist AL, Insolia R, Pedrazzini M, Ferrandi C, De Ferrari GM, Vicentini A, Yang P, Roden DM, George AL Jr, Schwartz PJ. KCNH2-K897T is a genetic modifier of latent congenital long-QT syndrome. Circulation. 2005;112:1251-1258
6. Westenskow P, Splawski I, Timothy KW, Keating MT, Sanguinetti MC. Compound mutations: a common cause of severe long-QT syndrome. Circulation. 2004;109:1834-1841
7. Schwartz PJ, Wolf S. QT interval prolongation as predictor of sudden death in patients with myocardial infarction. Circulation. 1978;57: 1074-1077
8. Chugh SS, Reinier K, Singh T, Uy-Evanado A, Socoteanu C, Peters D, Mariani R, Gunson K, Jui J. Determinants of prolonged QT interval and their contribution to sudden death risk in coronary artery disease: the Oregon Sudden Unexpected Death Study. Circulation. 2009;119: 663-670
9. Arking DE, Pfeufer A, Post W, Kao WH, Newton-Cheh C, Ikeda M, West K, Kashuk C, Akyol M, Perz S, Jalilzadeh S, Illig T, Gieger C, Guo CY, Larson MG, Wichmann HE, Marban E, O'Donnell CJ, Hirschhorn JN, Kaab S, Spooner PM, Meitinger T, Chakravarti A. A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization. Nat Genet. 2006;38:644-651
10. Aarnoudse AJ, Newton-Cheh C, De Bakker PI, Straus SM, Kors JA, Hofman A, Uitterlinden AG, Witteman JC, Stricker BH. Common NOS1AP variants are associated with a prolonged QTc interval in the Rotterdam Study. Circulation. 2007;116:10-16
11. Post W, Shen H, Damcott C, Arking DE, Kao WH, Sack PA, Ryan KA, Chakravarti A, Mitchell BD, Shuldiner AR. Associations between genetic variants in the NOS1AP (CAPON) gene and cardiac repolarization in the old order Amish. Hum Hered. 2007;64:214-219
12. Raitakari OT, Blom-Nyholm J, Koskinen TA, Kahonen M, Viikari JS, Lehtimaki T. Common variation in NOS1AP and KCNH2 genes and QT interval duration in young adults: the Cardiovascular Risk in Young Finns Study. Ann Med. 2008;41:144-151
13. Tobin MD, Kahonen M, Braund P, Nieminen T, Hajat C, Tomaszewski M, Viik J, Lehtinen R, Ng GA, Macfarlane PW, Burton PR, Lehtimaki T, Samani NJ. Gender and effects of a common genetic variant in the NOS1 regulator NOS1AP on cardiac repolarization in 3761 individuals from two independent populations. Int J Epidemiol. 2008;37:1132-1141
14. Lehtinen AB, Newton-Cheh C, Ziegler JT, Langefeld CD, Freedman BI, Daniel KR, Herrington DM, Bowden DW. Association of NOS1AP genetic variants with QT interval duration in families from the Diabetes Heart Study. Diabetes. 2008;57:1108-1114
15. Arking DE, Khera A, Xing C, Kao WH, Post W, Boerwinkle E, Chakravarti A. Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population. PLoS ONE. 2009; 4:e4333
16. Eijgelsheim M, Aarnoudse AL, Rivadeneira F, Kors JA, Witteman JC, Hofman A, van Duijn CM, Uitterlinden AG, Stricker BH. Identification of a common variant at the NOS1AP locus strongly associated to QT-interval duration. Hum Mol Genet. 2009;18:347-357
17. Newton-Cheh C, Eijgelsheim M, Rice KM, De Bakker PI, Yin X, Estrada K, Bis JC, Marciante K, Rivadeneira F, Noseworthy PA, Sotoodehnia N, Smith NL, Rotter JI, Kors JA, Witteman JC, Hofman A, Heckbert SR, O'Donnell CJ, Uitterlinden AG, Psaty BM, Lumley T, Larson MG, Stricker BH. Common variants at ten loci influence QT interval duration in the QTGEN Study. Nat Genet. 2009;41:399-406
18. Pfeufer A, Sanna S, Arking DE, Muller M, Gateva V, Fuchsberger C, Ehret GB, Orru M, Pattaro C, Kottgen A, Perz S, Usala G, Barbalic M, Li M, Putz B, Scuteri A, Prineas RJ, Sinner MF, Gieger C, Najjar SS, Kao WH, Muhleisen TW, Dei M, Happle C, Mohlenkamp S, Crisponi L, Erbel R, Jockel KH, Naitza S, Steinbeck G, Marroni F, Hicks AA, Lakatta E, Muller-Myhsok B, Pramstaller PP, Wichmann HE, Schlessinger D, Boer-winkle E, Meitinger T, Uda M, Coresh J, Kaab S, Abecasis GR, Chakravarti A. Common variants at ten loci modulate the QT interval duration in the QTSCD Study. Nat Genet. 2009;41:407-414
19. Kao WH, Arking DE, Post W, Rea TD, Sotoodehnia N, Prineas RJ, Bishe B, Doan BQ, Boerwinkle E, Psaty BM, Tomaselli GF, Coresh J, Siscovick DS, Marban E, Spooner PM, Burke GL, Chakravarti A. Genetic variations in nitric oxide synthase 1 adaptor protein are associated with sudden cardiac death in US white community-based populations. Circulation. 2009;119: 940-951
20. Becker ML, Visser LE, Newton-Cheh C, Hofman A, Uitterlinden AG, Witteman JC, Stricker BH. A common NOS1AP genetic polymorphism is associated with increased cardiovascular mortality in users of dihydropyridine calcium channel blockers. Br J Clin Pharmacol. 2009;67:61-67
21. Brink PA, Crotti L, Corfield V, Goosen A, Durrheim G, Hedley P, Heradien M, Geldenhuys G, Vanoli E, Bacchini S, Spazzolini C, Lun-dquist AL, Roden DM, George AL Jr, Schwartz PJ. Phenotypic variability and unusual clinical severity of congenital long-QT syndrome in a founder population. Circulation. 2005;112:2602-2610
22. Priori SG, Schwartz PJ, Napolitano C, Bloise R, Ronchetti E, Grillo M, Vicentini A, Spazzolini C, Nastoli J, Bottelli G, Folli R, Cappelletti D. Risk stratification in the long-QT syndrome. N Engl J Med. 2003;348: 1866-1874
23. Schwartz PJ, Priori SG, Spazzolini C, Moss AJ, Vincent GM, Napolitano C, Denjoy I, Guicheney P, Breithardt G, Keating MT, Towbin JA, Beggs AH, Brink P, Wilde AA, Toivonen L, Zareba W, Robinson JL, Timothy KW, Corfield V, Wattanasirichaigoon D, Corbett C, Haverkamp W, Schulze-Bahr E, Lehmann MH, Schwartz K, Coumel P, Bloise R. Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation. 2001; 103:89-95
24. Moss AJ, Shimizu W, Wilde AA, Towbin JA, Zareba W, Robinson JL, Qi M, Vincent GM, Ackerman MJ, Kaufman ES, Hofman N, Seth R, Kamakura S, Miyamoto Y, Goldenberg I, Andrews ML, McNitt S. Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene. Circulation. 2007;115:2481-2489
25. Newton-Cheh C, Guo CY, Wang TJ, O'Donnell CJ, Levy D, Larson MG. Genome-wide association study of electrocardiographic and heart rate variability traits: the Framingham Heart Study. BMC Med Genet. 2007; 8(suppl I):S7
26. Martin ER, Monks SA, Warren LL, Kaplan NL. A test for linkage and association in general pedigrees: the pedigree disequilibrium test. Am J Hum Genet. 2000;67:146-154
27. Hardy SW, Weir BS, Kaplan NL, Martin ER. Analysis of single nucle-otide polymorphisms in candidate genes using the pedigree disequilibrium test. Genet Epidemiol. 2001;21(suppl 1):S441-S446
28. Nyholt DR. A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet. 2004;74:765-769
29. Li J, Ji L. Adjusting multiple testing in multilocus analyses using the eigenvalues of a correlation matrix. Heredity. 2005;95:221-227
30. Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R, Ward R, Lander ES, Daly MJ, Altshuler D The structure of haplotype blocks in the human genome. Science. 2002; 296:2225-2229.
31. Crotti L, Spazzolini C, Schwartz PJ, Shimizu W, Denjoy I, Schulze-Bahr E, Zaklyazminskaya EV, Swan H, Ackerman MJ, Moss AJ, Wilde AA, Horie M, Brink PA, Insolia R, De Ferrari GM, Crimi G. The common long-QT syndrome mutation KCNQ1/A341V causes unusually severe clinical manifestations in patients with different ethnic backgrounds: toward a mutation-specific risk stratification. Circulation. 2007;116: 2366-2375
32. Wratten NS, Memoli H, Huang Y, Dulencin AM, Matteson PG, Cor-nacchia MA, Azaro MA, Messenger J, Hayter JE, Bassett AS, Buyske S, Millonig JH, Vieland VJ, Brzustowicz LM. Identification of a schizophrenia-associated functional noncoding variant in NOS1AP. Am J Psychiatry. 2009;166:434-441
33. Chang KC, Barth AS, Sasano T, Kizana E, Kashiwakura Y, Zhang Y, Foster DB, Marban E. CAPON modulates cardiac repolarization via neuronal nitric oxide synthase signaling in the heart. Proc Natl Acad Sci U S A. 2008;105:4477-4482