Large-scale gene-centric analysis identifies polymorphisms for resistant hypertension

Vanessa Fontana, Caitrin W McDonough, Yan Gong, Nihal M El Rouby, Ana Caroline C Sá, Kent D Taylor, Y-D Ida Chen, John G Gums, Arlene B Chapman, Stephen T Turner, Carl J Pepine, Julie A Johnson, Rhonda M Cooper-DeHoff, Vanessa Fontana, Caitrin W McDonough, Yan Gong, Nihal M El Rouby, Ana Caroline C Sá, Kent D Taylor, Y-D Ida Chen, John G Gums, Arlene B Chapman, Stephen T Turner, Carl J Pepine, Julie A Johnson, Rhonda M Cooper-DeHoff

Abstract

Background: Resistant hypertension (RHTN), defined by lack of blood pressure (BP) control despite treatment with at least 3 antihypertensive drugs, increases cardiovascular risk compared with controlled hypertension. Yet, there are few data on genetic variants associated with RHTN.

Methods and results: We used a gene-centric array containing ≈50 000 single-nucleotide polymorphisms (SNPs) to identify polymorphisms associated with RHTN in hypertensive participants with coronary artery disease (CAD) from INVEST-GENES (the INnternational VErapamil-SR Trandolapril STudy-GENEtic Substudy). RHTN was defined as BP≥140/90 on 3 drugs, or any BP on 4 or more drugs. Logistic regression analysis was performed in European Americans (n=904) and Hispanics (n=837), using an additive model adjusted for age, gender, randomized treatment assignment, body mass index, principal components for ancestry, and other significant predictors of RHTN. Replication of the top SNP was conducted in 241 European American women from WISE (Women's Ischemia Syndrome Evaluation), where RHTN was defined similarly. To investigate the functional effect of rs12817819, mRNA expression was measured in whole blood. We found ATP2B1 rs12817819 associated with RHTN in both INVEST European Americans (P-value=2.44×10(-3), odds ratio=1.57 [1.17 to 2.01]) and INVEST Hispanics (P=7.69×10(-4), odds ratio=1.76 [1.27 to 2.44]). A consistent trend was observed at rs12817819 in WISE, and the INVEST-WISE meta-analysis result reached chip-wide significance (P=1.60×10(-6), odds ratio=1.65 [1.36 to 1.95]). Expression analyses revealed significant differences in ATP2B1 expression by rs12817819 genotype.

Conclusions: The ATP2B1 rs12817819 A allele is associated with increased risk for RHTN in hypertensive participants with documented CAD or suspected ischemic heart disease.

Clinical trial registration url: www.clinicaltrials.gov; Unique identifiers: NCT00133692 (INVEST), NCT00000554 (WISE).

Keywords: genetics; hypertension; pharmacology; resistant hypertension.

© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Figures

Figure 1.
Figure 1.
Adjusted odds ratios and 95% CIs for resistant hypertension risk for ATP2B1 rs12817819 in INternational VErapamil SR Trandolapril STudy (INVEST) European Americans (EA), INVEST Hispanics, The Women's Ischemia Syndrome Evaluation (WISE) study, and meta‐analysis.
Figure 2.
Figure 2.
Genotype‐specific odds ratios and 95% CI for resistant hypertension risk for ATP2B1 rs12817819 in INternational VErapamil SR Trandolapril STudy (INVEST) European Americans (EA), INVEST Hispanics, and The Women's Ischemia Syndrome Evaluation (WISE). WISE AA genotype specific odds ratio and 95% CI was unestimable due to low genotype count (n=2).
Figure 3.
Figure 3.
Relative gene expression of ATP2B1 by rs12817819 genotype in 45 European Americans (EA) from the Pharmacogenomic Evaluation of Antihypertensive Responses study. Expression data are normalized to β‐2‐microglobulin. Error bars indicate standard error.

References

    1. Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, White A, Cushman WC, White W, Sica D, Ferdinand K, Giles TD, Falkner B, Carey RM. Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension. 2008; 51:1403-1419.
    1. Persell SD. Prevalence of resistant hypertension in the United States, 2003–2008. Hypertension. 2011; 57:1076-1080.
    1. Gupta AK, Nasothimiou EG, Chang CL, Sever PS, Dahlöf B, Poulter NRASCOT Investigators. Baseline predictors of resistant hypertension in the Anglo‐Scandinavian Cardiac Outcome Trial (ASCOT): a risk score to identify those at high‐risk. J Hypertens. 2011; 29:2004-2013.
    1. Smith SM, Huo T, Delia Johnson B, Bittner V, Kelsey SF, Vido Thompson D, Noel Bairey Merz C, Pepine CJ, Cooper‐Dehoff RM. Cardiovascular and mortality risk of apparent resistant hypertension in women with suspected myocardial ischemia: a report from the NHLBI‐sponsored WISE study. J Am Heart Assoc. 2014; 3:e000660.
    1. Smith SM, Gong Y, Handberg E, Messerli FH, Bakris GL, Ahmed A, Bavry AA, Pepine CJ, Cooper‐Dehoff RM. Predictors and outcomes of resistant hypertension among patients with coronary artery disease and hypertension. J Hypertens. 2014; 32:635-643.
    1. Cuspidi C, Macca G, Sampieri L, Michev I, Salerno M, Fusi V, Severgnini B, Meani S, Magrini F, Zanchetti A. High prevalence of cardiac and extracardiac target organ damage in refractory hypertension. J Hypertens. 2001; 19:2063-2070.
    1. Daugherty SL, Powers JD, Magid DJ, Tavel HM, Masoudi FA, Margolis KL, O'Connor PJ, Selby JV, Ho PM. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation. 2012; 125:1635-1642.
    1. Pierdomenico SD, Lapenna D, Bucci A, Di Tommaso R, Di Mascio R, Manente BM, Caldarella MP, Neri M, Cuccurullo F, Mezzetti A. Cardiovascular outcome in treated hypertensive patients with responder, masked, false resistant, and true resistant hypertension. Am J Hypertens. 2005; 18:1422-1428.
    1. Levy D, Ehret GB, Rice K, Verwoert GC, Launer LJ, Dehghan A, Glazer NL, Morrison AC, Johnson AD, Aspelund T, Aulchenko Y, Lumley T, Köttgen A, Vasan RS, Rivadeneira F, Eiriksdottir G, Guo X, Arking DE, Mitchell GF, Mattace‐Raso FU, Smith AV, Taylor K, Scharpf RB, Hwang SJ, Sijbrands EJ, Bis J, Harris TB, Ganesh SK, O'Donnell CJ, Hofman A, Rotter JI, Coresh J, Benjamin EJ, Uitterlinden AG, Heiss G, Fox CS, Witteman JC, Boerwinkle E, Wang TJ, Gudnason V, Larson MG, Chakravarti A, Psaty BM, van Duijn CM. Genome‐wide association study of blood pressure and hypertension. Nat Genet. 2009; 41:677-687.
    1. Ganesh SK, Tragante V, Guo W, Guo Y, Lanktree MB, Smith EN, Johnson T, Castillo BA, Barnard J, Baumert J, Chang YP, Elbers CC, Farrall M, Fischer ME, Franceschini N, Gaunt TR, Gho JM, Gieger C, Gong Y, Isaacs A, Kleber ME, Mateo Leach I, McDonough CW, Meijs MF, Mellander O, Molony CM, Nolte IM, Padmanabhan S, Price TS, Rajagopalan R, Shaffer J, Shah S, Shen H, Soranzo N, van der Most PJ, Van Iperen EP, Van Setten JA, Vonk JM, Zhang L, Beitelshees AL, Berenson GS, Bhatt DL, Boer JM, Boerwinkle E, Burkley B, Burt A, Chakravarti A, Chen W, Cooper‐Dehoff RM, Curtis SP, Dreisbach A, Duggan D, Ehret GB, Fabsitz RR, Fornage M, Fox E, Furlong CE, Gansevoort RT, Hofker MH, Hovingh GK, Kirkland SA, Kottke‐Marchant K, Kutlar A, Lacroix AZ, Langaee TY, Li YR, Lin H, Liu K, Maiwald S, Malik R, Murugesan G, Newton‐Cheh C, O'Connell JR, Onland‐Moret NC, Ouwehand WH, Palmas W, Penninx BW, Pepine CJ, Pettinger M, Polak JF, Ramachandran VS, Ranchalis J, Redline S, Ridker PM, Rose LM, Scharnag H, Schork NJ, Shimbo D, Shuldiner AR, Srinivasan SR, Stolk RP, Taylor HA, Thorand B, Trip MD, van Duijn CM, Verschuren WM, Wijmenga C, Winkelmann BR, Wyatt S, Young JH, Boehm BO, Caulfield MJ, Chasman DI, Davidson KW, Doevendans PA, Fitzgerald GA, Gums JG, Hakonarson H, Hillege HL, Illig T, Jarvik GP, Johnson JA, Kastelein JJ, Koenig W, Marz W, Mitchell BD, Murray SS, Oldehinkel AJ, Rader DJ, Reilly MP, Reiner AP, Schadt EE, Silverstein RL, Snieder H, Stanton AV, Uitterlinden AG, van der Harst P, van der Schouw YT, Samani NJ, Johnson AD, Munroe PB, de Bakker PI, Zhu X, Levy D, Keating BJ, Asselbergs FWCARDIOGRAM META, Study LC. Loci influencing blood pressure identified using a cardiovascular gene‐centric array. Hum Mol Genet. 2013; 22:1663-1678.
    1. Gong Y, McDonough CW, Wang Z, Hou W, Cooper‐DeHoff RM, Langaee TY, Beitelshees AL, Chapman AB, Gums JG, Bailey KR, Boerwinkle E, Turner ST, Johnson JA. Hypertension susceptibility loci and blood pressure response to antihypertensives: results from the pharmacogenomic evaluation of antihypertensive responses study. Circ Cardiovasc Genet. 2012; 5:686-691.
    1. Silva PS, Fontana V, Luizon MR, Lacchini R, Silva WA, Biagi C, Tanus‐Santos JE. eNOS and BDKRB2 genotypes affect the antihypertensive responses to enalapril. Eur J Clin Pharmacol. 2013; 69:167-177.
    1. Keating BJ, Tischfield S, Murray SS, Bhangale T, Price TS, Glessner JT, Galver L, Barrett JC, Grant SF, Farlow DN, Chandrupatla HR, Hansen M, Ajmal S, Papanicolaou GJ, Guo Y, Li M, Derohannessian S, de Bakker PI, Bailey SD, Montpetit A, Edmondson AC, Taylor K, Gai X, Wang SS, Fornage M, Shaikh T, Groop L, Boehnke M, Hall AS, Hattersley AT, Frackelton E, Patterson N, Chiang CW, Kim CE, Fabsitz RR, Ouwehand W, Price AL, Munroe P, Caulfield M, Drake T, Boerwinkle E, Reich D, Whitehead AS, Cappola TP, Samani NJ, Lusis AJ, Schadt E, Wilson JG, Koenig W, McCarthy MI, Kathiresan S, Gabriel SB, Hakonarson H, Anand SS, Reilly M, Engert JC, Nickerson DA, Rader DJ, Hirschhorn JN, Fitzgerald GA. Concept, design and implementation of a cardiovascular gene‐centric 50 k SNP array for large‐scale genomic association studies. PLoS One. 2008; 3:e3583.
    1. Pepine CJ, Handberg EM, Cooper‐DeHoff RM, Marks RG, Kowey P, Messerli FH, Mancia G, Cangiano JL, Garcia‐Barreto D, Keltai M, Erdine S, Bristol HA, Kolb HR, Bakris GL, Cohen JD, Parmley WWINVEST Investigators. A calcium antagonist vs a non‐calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil‐Trandolapril Study (INVEST): a randomized controlled trial. JAMA. 2003; 290:2805-2816.
    1. Pepine CJ, Handberg‐Thurmond E, Marks RG, Conlon M, Cooper‐DeHoff R, Volkers P, Zellig P. Rationale and design of the International Verapamil SR/Trandolapril Study (INVEST): An internet‐based randomized trial in coronary artery disease patients with hypertension. J Am Coll Cardiol. 1998; 32:1228-1237.
    1. The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med. 1997; 157:2413-2446.
    1. Merz CN, Kelsey SF, Pepine CJ, Reichek N, Reis SE, Rogers WJ, Sharaf BL, Sopko G. The Women's Ischemia Syndrome Evaluation (WISE) study: Protocol design, methodology and feasibility report. J Am Coll Cardiol. 1999; 33:1453-1461.
    1. Andrisin TE, Humma LM, Johnson JA. Collection of genomic DNA by the noninvasive mouthwash method for use in pharmacogenetic studies. Pharmacotherapy. 2002; 22:954-960.
    1. Voight BF, Kang HM, Ding J, Palmer CD, Sidore C, Chines PS, Burtt NP, Fuchsberger C, Li Y, Erdmann J, Frayling TM, Heid IM, Jackson AU, Johnson T, Kilpelainen TO, Lindgren CM, Morris AP, Prokopenko I, Randall JC, Saxena R, Soranzo N, Speliotes EK, Teslovich TM, Wheeler E, Maguire J, Parkin M, Potter S, Rayner NW, Robertson N, Stirrups K, Winckler W, Sanna S, Mulas A, Nagaraja R, Cucca F, Barroso I, Deloukas P, Loos RJ, Kathiresan S, Munroe PB, Newton‐Cheh C, Pfeufer A, Samani NJ, Schunkert H, Hirschhorn JN, Altshuler D, McCarthy MI, Abecasis GR, Boehnke M. The metabochip, a custom genotyping array for genetic studies of metabolic, cardiovascular, and anthropometric traits. PLoS Genet. 2012; 8:e1002793.
    1. Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D. Principal components analysis corrects for stratification in genome‐wide association studies. Nat Genet. 2006; 38:904-909.
    1. Purcell S, Neale B, Todd‐Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC. Plink: A tool set for whole‐genome association and population‐based linkage analyses. Am J Hum Genet. 2007; 81:559-575.
    1. Willer CJ, Li Y, Abecasis GR. Metal: fast and efficient meta‐analysis of genomewide association scans. Bioinformatics. 2010; 26:2190-2191.
    1. Saxena R, Elbers CC, Guo Y, Peter I, Gaunt TR, Mega JL, Lanktree MB, Tare A, Castillo BA, Li YR, Johnson T, Bruinenberg M, Gilbert‐Diamond D, Rajagopalan R, Voight BF, Balasubramanyam A, Barnard J, Bauer F, Baumert J, Bhangale T, Böhm BO, Braund PS, Burton PR, Chandrupatla HR, Clarke R, Cooper‐DeHoff RM, Crook ED, Davey‐Smith G, Day IN, de Boer A, de Groot MC, Drenos F, Ferguson J, Fox CS, Furlong CE, Gibson Q, Gieger C, Gilhuijs‐Pederson LA, Glessner JT, Goel A, Gong Y, Grant SF, Grobbee DE, Hastie C, Humphries SE, Kim CE, Kivimaki M, Kleber M, Meisinger C, Kumari M, Langaee TY, Lawlor DA, Li M, Lobmeyer MT, Maitland‐van der Zee AH, Meijs MF, Molony CM, Morrow DA, Murugesan G, Musani SK, Nelson CP, Newhouse SJ, O'Connell JR, Padmanabhan S, Palmen J, Patel SR, Pepine CJ, Pettinger M, Price TS, Rafelt S, Ranchalis J, Rasheed A, Rosenthal E, Ruczinski I, Shah S, Shen H, Silbernagel G, Smith EN, Spijkerman AW, Stanton A, Steffes MW, Thorand B, Trip M, van der Harst P, van der A DL, van Iperen EP, van Setten J, van Vliet‐Ostaptchouk JV, Verweij N, Wolffenbuttel BH, Young T, Zafarmand MH, Zmuda JM, Boehnke M, Altshuler D, McCarthy M, Kao WH, Pankow JS, Cappola TP, Sever P, Poulter N, Caulfield M, Dominiczak A, Shields DC, Bhatt DL, Bhatt D, Zhang L, Curtis SP, Danesh J, Casas JP, van der Schouw YT, Onland‐Moret NC, Doevendans PA, Dorn GW, Farrall M, FitzGerald GA, Hamsten A, Hegele R, Hingorani AD, Hofker MH, Huggins GS, Illig T, Jarvik GP, Johnson JA, Klungel OH, Knowler WC, Koenig W, März W, Meigs JB, Melander O, Munroe PB, Mitchell BD, Bielinski SJ, Rader DJ, Reilly MP, Rich SS, Rotter JI, Saleheen D, Samani NJ, Schadt EE, Shuldiner AR, Silverstein R, Kottke‐Marchant K, Talmud PJ, Watkins H, Asselbergs FW, Asselbergs F, de Bakker PI, McCaffery J, Wijmenga C, Sabatine MS, Wilson JG, Reiner A, Bowden DW, Hakonarson H, Siscovick DS, Keating BJGroup LAR, consortium D. Large‐scale gene‐centric meta‐analysis across 39 studies identifies type 2 diabetes loci. Am J Hum Genet. 2012; 90:410-425.
    1. Johnson JA, Boerwinkle E, Zineh I, Chapman AB, Bailey K, Cooper‐DeHoff RM, Gums J, Curry RW, Gong Y, Beitelshees AL, Schwartz G, Turner ST. Pharmacogenomics of antihypertensive drugs: rationale and design of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study. Am Heart J. 2009; 157:442-449.
    1. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real‐time quantitative PCR and the 2(‐Delta Delta C(T)) Method. Methods. 2001; 25:402-408.
    1. Ehret GB, Munroe PB, Rice KM, Bochud M, Johnson AD, Chasman DI, Smith AV, Tobin MD, Verwoert GC, Hwang SJ, Pihur V, Vollenweider P, O'Reilly PF, Amin N, Bragg‐Gresham JL, Teumer A, Glazer NL, Launer L, Zhao JH, Aulchenko Y, Heath S, Sõber S, Parsa A, Luan J, Arora P, Dehghan A, Zhang F, Lucas G, Hicks AA, Jackson AU, Peden JF, Tanaka T, Wild SH, Rudan I, Igl W, Milaneschi Y, Parker AN, Fava C, Chambers JC, Fox ER, Kumari M, Go MJ, van der Harst P, Kao WH, Sjögren M, Vinay DG, Alexander M, Tabara Y, Shaw‐Hawkins S, Whincup PH, Liu Y, Shi G, Kuusisto J, Tayo B, Seielstad M, Sim X, Nguyen KD, Lehtimäki T, Matullo G, Wu Y, Gaunt TR, Onland‐Moret NC, Cooper MN, Platou CG, Org E, Hardy R, Dahgam S, Palmen J, Vitart V, Braund PS, Kuznetsova T, Uiterwaal CS, Adeyemo A, Palmas W, Campbell H, Ludwig B, Tomaszewski M, Tzoulaki I, Palmer ND, Aspelund T, Garcia M, Chang YP, O'Connell JR, Steinle NI, Grobbee DE, Arking DE, Kardia SL, Morrison AC, Hernandez D, Najjar S, McArdle WL, Hadley D, Brown MJ, Connell JM, Hingorani AD, Day IN, Lawlor DA, Beilby JP, Lawrence RW, Clarke R, Hopewell JC, Ongen H, Dreisbach AW, Li Y, Young JH, Bis JC, Kähönen M, Viikari J, Adair LS, Lee NR, Chen MH, Olden M, Pattaro C, Bolton JA, Köttgen A, Bergmann S, Mooser V, Chaturvedi N, Frayling TM, Islam M, Jafar TH, Erdmann J, Kulkarni SR, Bornstein SR, Grässler J, Groop L, Voight BF, Kettunen J, Howard P, Taylor A, Guarrera S, Ricceri F, Emilsson V, Plump A, Barroso I, Khaw KT, Weder AB, Hunt SC, Sun YV, Bergman RN, Collins FS, Bonnycastle LL, Scott LJ, Stringham HM, Peltonen L, Perola M, Vartiainen E, Brand SM, Staessen JA, Wang TJ, Burton PR, Soler Artigas M, Dong Y, Snieder H, Wang X, Zhu H, Lohman KK, Rudock ME, Heckbert SR, Smith NL, Wiggins KL, Doumatey A, Shriner D, Veldre G, Viigimaa M, Kinra S, Prabhakaran D, Tripathy V, Langefeld CD, Rosengren A, Thelle DS, Corsi AM, Singleton A, Forrester T, Hilton G, McKenzie CA, Salako T, Iwai N, Kita Y, Ogihara T, Ohkubo T, Okamura T, Ueshima H, Umemura S, Eyheramendy S, Meitinger T, Wichmann HE, Cho YS, Kim HL, Lee JY, Scott J, Sehmi JS, Zhang W, Hedblad B, Nilsson P, Smith GD, Wong A, Narisu N, Stancáková A, Raffel LJ, Yao J, Kathiresan S, O'Donnell CJ, Schwartz SM, Ikram MA, Longstreth WT, Mosley TH, Seshadri S, Shrine NR, Wain LV, Morken MA, Swift AJ, Laitinen J, Prokopenko I, Zitting P, Cooper JA, Humphries SE, Danesh J, Rasheed A, Goel A, Hamsten A, Watkins H, Bakker SJ, van Gilst WH, Janipalli CS, Mani KR, Yajnik CS, Hofman A, Mattace‐Raso FU, Oostra BA, Demirkan A, Isaacs A, Rivadeneira F, Lakatta EG, Orru M, Scuteri A, Ala‐Korpela M, Kangas AJ, Lyytikäinen LP, Soininen P, Tukiainen T, Würtz P, Ong RT, Dörr M, Kroemer HK, Völker U, Völzke H, Galan P, Hercberg S, Lathrop M, Zelenika D, Deloukas P, Mangino M, Spector TD, Zhai G, Meschia JF, Nalls MA, Sharma P, Terzic J, Kumar MV, Denniff M, Zukowska‐Szczechowska E, Wagenknecht LE, Fowkes FG, Charchar FJ, Schwarz PE, Hayward C, Guo X, Rotimi C, Bots ML, Brand E, Samani NJ, Polasek O, Talmud PJ, Nyberg F, Kuh D, Laan M, Hveem K, Palmer LJ, van der Schouw YT, Casas JP, Mohlke KL, Vineis P, Raitakari O, Ganesh SK, Wong TY, Tai ES, Cooper RS, Laakso M, Rao DC, Harris TB, Morris RW, Dominiczak AF, Kivimaki M, Marmot MG, Miki T, Saleheen D, Chandak GR, Coresh J, Navis G, Salomaa V, Han BG, Zhu X, Kooner JS, Melander O, Ridker PM, Bandinelli S, Gyllensten UB, Wright AF, Wilson JF, Ferrucci L, Farrall M, Tuomilehto J, Pramstaller PP, Elosua R, Soranzo N, Sijbrands EJ, Altshuler D, Loos RJ, Shuldiner AR, Gieger C, Meneton P, Uitterlinden AG, Wareham NJ, Gudnason V, Rotter JI, Rettig R, Uda M, Strachan DP, Witteman JC, Hartikainen AL, Beckmann JS, Boerwinkle E, Vasan RS, Boehnke M, Larson MG, Järvelin MR, Psaty BM, Abecasis GR, Chakravarti A, Elliott P, van Duijn CM, Newton‐Cheh C, Levy D, Caulfield MJ, Johnson TStudies ICfBPG‐WA, Consortium C, Consortium C, Consortium K, Consortium E, Consortium C‐H. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature. 2011; 478:103-109.
    1. Lu X, Wang L, Chen S, He L, Yang X, Shi Y, Cheng J, Zhang L, Gu CC, Huang J, Wu T, Ma Y, Li J, Cao J, Chen J, Ge D, Fan Z, Li Y, Zhao L, Li H, Zhou X, Chen L, Liu D, Duan X, Hao Y, Lu F, Liu Z, Yao C, Shen C, Pu X, Yu L, Fang X, Xu L, Mu J, Wu X, Zheng R, Wu N, Zhao Q, Liu X, Wang M, Yu D, Hu D, Ji X, Guo D, Sun D, Wang Q, Yang Y, Liu F, Mao Q, Liang X, Ji J, Chen P, Mo X, Li D, Chai G, Tang Y, Li X, Du Z, Dou C, Yang Z, Meng Q, Wang D, Wang R, Yang J, Schunkert H, Samani NJ, Kathiresan S, Reilly MP, Erdmann J, Peng X, Chen R, Qiang B, Gu DConsortium CADG‐WRAM‐AC. Genome‐wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease. Nat Genet. 2012; 44:890-894.
    1. Carafoli E. Biogenesis: plasma membrane calcium ATPase: 15 years of work on the purified enzyme. FASEB J. 1994; 8:993-1002.
    1. Monteith GR, Kable EP, Kuo TH, Roufogalis BD. Elevated plasma membrane and sarcoplasmic reticulum Ca2+ pump mRNA levels in cultured aortic smooth muscle cells from spontaneously hypertensive rats. Biochem Biophys Res Commun. 1997; 230:344-346.
    1. Kobayashi Y, Hirawa N, Tabara Y, Muraoka H, Fujita M, Miyazaki N, Fujiwara A, Ichikawa Y, Yamamoto Y, Ichihara N, Saka S, Wakui H, Yoshida S, Yatsu K, Toya Y, Yasuda G, Kohara K, Kita Y, Takei K, Goshima Y, Ishikawa Y, Ueshima H, Miki T, Umemura S. Mice lacking hypertension candidate gene ATP2B1 in vascular smooth muscle cells show significant blood pressure elevation. Hypertension. 2012; 59:854-860.
    1. Shin YB, Lim JE, Ji SM, Lee HJ, Park SY, Hong KW, Lim M, McCarthy MI, Lee YH, Oh B. Silencing of ATP2B1 increases blood pressure through vasoconstriction. J Hypertens. 2013; 31:1575-1583.
    1. Tsai FJ, Yang CF, Chen CC, Chuang LM, Lu CH, Chang CT, Wang TY, Chen RH, Shiu CF, Liu YM, Chang CC, Chen P, Chen CH, Fann CS, Chen YT, Wu JY. A genome‐wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese. PLoS Genet. 2010; 6:e1000847.
    1. Saade S, Cazier JB, Ghassibe‐Sabbagh M, Youhanna S, Badro DA, Kamatani Y, Hager J, Yeretzian JS, El‐Khazen G, Haber M, Salloum AK, Douaihy B, Othman R, Shasha N, Kabbani S, Bayeh HE, Chammas E, Farrall M, Gauguier D, Platt DE, Zalloua PAFGENtCARD consortium. Large scale association analysis identifies three susceptibility loci for coronary artery disease. PLoS One. 2011; 6:e29427.
    1. Ellis JA, Lamantia A, Chavez R, Scurrah KJ, Nichols CG, Harrap SB. Genes controlling postural changes in blood pressure: comprehensive association analysis of ATP‐sensitive potassium channel genes KCNJ8 and ABCC9. Physiol Genomics. 2010; 40:184-188.
    1. Vasan RS, Glazer NL, Felix JF, Lieb W, Wild PS, Felix SB, Watzinger N, Larson MG, Smith NL, Dehghan A, Grosshennig A, Schillert A, Teumer A, Schmidt R, Kathiresan S, Lumley T, Aulchenko YS, König IR, Zeller T, Homuth G, Struchalin M, Aragam J, Bis JC, Rivadeneira F, Erdmann J, Schnabel RB, Dörr M, Zweiker R, Lind L, Rodeheffer RJ, Greiser KH, Levy D, Haritunians T, Deckers JW, Stritzke J, Lackner KJ, Völker U, Ingelsson E, Kullo I, Haerting J, O'Donnell CJ, Heckbert SR, Stricker BH, Ziegler A, Reffelmann T, Redfield MM, Werdan K, Mitchell GF, Rice K, Arnett DK, Hofman A, Gottdiener JS, Uitterlinden AG, Meitinger T, Blettner M, Friedrich N, Wang TJ, Psaty BM, van Duijn CM, Wichmann HE, Munzel TF, Kroemer HK, Benjamin EJ, Rotter JI, Witteman JC, Schunkert H, Schmidt H, Völzke H, Blankenberg S. Genetic variants associated with cardiac structure and function: a meta‐analysis and replication of genome‐wide association data. JAMA. 2009; 302:168-178.
    1. Mackness MI, Mackness B, Durrington PN. Paraoxonase and coronary heart disease. Atherosclerosis Suppl. 2002; 3:49-55.
    1. Wang M, Lang X, Zou L, Huang S, Xu Z. Four genetic polymorphisms of paraoxonase gene and risk of coronary heart disease: a meta‐analysis based on 88 case–control studies. Atherosclerosis. 2011; 214:377-385.
    1. Wheeler JG, Keavney BD, Watkins H, Collins R, Danesh J. Four paraoxonase gene polymorphisms in 11212 cases of coronary heart disease and 12786 controls: meta‐analysis of 43 studies. Lancet. 2004; 363:689-695.
    1. Voetsch B, Benke KS, Damasceno BP, Siqueira LH, Loscalzo J. Paraoxonase 192 Gln–>Arg polymorphism: an independent risk factor for nonfatal arterial ischemic stroke among young adults. Stroke. 2002; 33:1459-1464.
    1. Topic E, Simundic AM, Ttefanovic M, Demarin V, Vukovic V, Lovrencic‐Huzjan A, Zuntar I. Polymorphism of apoprotein E (APOE), methylenetetrahydrofolate reductase (MTHFR) and paraoxonase (PON1) genes in patients with cerebrovascular disease. Clin Chem Lab Med. 2001; 39:346-350.
    1. Figueiredo VN, Yugar‐Toledo JC, Martins LC, Martins LB, de Faria AP, de Haro Moraes C, Sierra C, Coca A, Moreno H. Vascular stiffness and endothelial dysfunction: correlations at different levels of blood pressure. Blood Press. 2012; 21:31-38.
    1. Pabuccu T, Baris N, Ozpelit E, Akdeniz B, Guneri S. The relationship between resistant hypertension and arterial stiffness. Clin Exp Hypertens. 2012; 34:57-62.
    1. Lynch AI, Irvin MR, Davis BR, Ford CE, Eckfeldt JH, Arnett DK. Genetic and adverse health outcome associations with treatment resistant hypertension in GenHat. Int J Hypertens. 2013; 2013:578578.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться