Pharmacogenomics in the Management of Pulmonary Arterial Hypertension: Current Perspectives

References

• Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004;351(14):1425–1436. doi:10.1056/NEJMra040291
   PubMed Web of Science ®Google Scholar
• Fessel JP, Loyd JE, Austin ED. The genetics of pulmonary arterial hypertension in the post-BMPR2 era. Pulm Circ. 2011;1(3):305–319. doi:10.4103/2045-8932.87293
   PubMedGoogle Scholar
• Galie N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the joint task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: association for European paediatric and congenital Cardiology (AEPC), international society for heart and lung transplantation (ISHLT). Eur Heart J. 2016;37(1):67–119. doi:10.1093/eurheartj/ehv317
   PubMed Web of Science ®Google Scholar
• Galie N, Channick RN, Frantz RP, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J. 2019;53(1):1801889. doi:10.1183/13993003.01889-2018
   PubMed Web of Science ®Google Scholar
• Halliday SJ, Hemnes AR. Identifying “super responders” in pulmonary arterial hypertension. Pulm Circ. 2017;7(2):300–311. doi:10.1177/2045893217697708
   PubMed Web of Science ®Google Scholar
• Galie N, Barbera JA, Frost AE, et al. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med. 2015;373(9):834–844. doi:10.1056/NEJMoa1413687
   PubMed Web of Science ®Google Scholar
• Barst RJ, Rubin LJ, Long WA, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med. 1996;334(5):296–301. doi:10.1056/NEJM199602013340504
   PubMed Web of Science ®Google Scholar
• D’Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med. 1991;115(5):343–349. doi:10.7326/0003-4819-115-5-343
   PubMed Web of Science ®Google Scholar
• Benza RL, Miller DP, Gomberg-Maitland M, et al. Predicting survival in pulmonary arterial hypertension: insights from the registry to evaluate early and long-term pulmonary arterial hypertension disease management (REVEAL). Circulation. 2010;122(2):164–172. doi:10.1161/CIRCULATIONAHA.109.898122
   PubMed Web of Science ®Google Scholar
• Gomberg-Maitland M, Glassner-Kolmin C, Watson S, et al. Survival in pulmonary arterial hypertension patients awaiting lung transplantation. J Heart Lung Transplant. 2013;32(12):1179–1186. doi:10.1016/j.healun.2013.08.016
   PubMed Web of Science ®Google Scholar
• Rich S, Brundage BH. High-dose calcium channel-blocking therapy for primary pulmonary hypertension: evidence for long-term reduction in pulmonary arterial pressure and regression of right ventricular hypertrophy. Circulation. 1987;76(1):135–141. doi:10.1161/01.CIR.76.1.135
   PubMed Web of Science ®Google Scholar
• Sitbon O, Humbert M, Jais X, et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation. 2005;111(23):3105–3111. doi:10.1161/CIRCULATIONAHA.104.488486
   PubMed Web of Science ®Google Scholar
• Kuhn KP, Byrne DW, Arbogast PG, Doyle TP, Loyd JE, Robbins IM. Outcome in 91 consecutive patients with pulmonary arterial hypertension receiving epoprostenol. Am J Respir Crit Care Med. 2003;167(4):580–586. doi:10.1164/rccm.200204-333OC
   PubMed Web of Science ®Google Scholar
• Johnson RF, Loyd JE, Mullican AL, Fink CA, Robbins IM. Long-term follow-up after conversion from intravenous epoprostenol to oral therapy with bosentan or sildenafil in 13 patients with pulmonary arterial hypertension. J Heart Lung Transplant. 2007;26(4):363–369. doi:10.1016/j.healun.2007.01.022
   PubMed Web of Science ®Google Scholar
• McLaughlin VV, Shillington A, Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation. 2002;106(12):1477–1482. doi:10.1161/01.CIR.0000029100.82385.58
   PubMed Web of Science ®Google Scholar
• Evans WE, McLeod HL. Pharmacogenomics--drug disposition, drug targets, and side effects. N Engl J Med. 2003;348(6):538–549. doi:10.1056/NEJMra020526
   PubMed Web of Science ®Google Scholar
• Soubrier F, Chung WK, Machado R, et al. Genetics and genomics of pulmonary arterial hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D13–21. doi:10.1016/j.jacc.2013.10.035
   PubMed Web of Science ®Google Scholar
• Newman JH, Rich S, Abman SH, et al. Enhancing insights into pulmonary vascular disease through a precision medicine approach. A Joint NHLBI-Cardiovascular medical research and education fund workshop report. Am J Respir Crit Care Med. 2017;195(12):1661–1670. doi:10.1164/rccm.201701-0150WS
   PubMed Web of Science ®Google Scholar
• Austin ED, West J, Loyd JE, Hemnes AR. Translational advances in the field of pulmonary hypertension molecular medicine of pulmonary arterial hypertension. From population genetics to precision medicine and gene editing. Am J Respir Crit Care Med. 2017;195(1):23–31. doi:10.1164/rccm.201605-0905PP
   PubMed Web of Science ®Google Scholar
• Erzurum S, Rounds SI, Stevens T, et al. Strategic plan for lung vascular research: an NHLBI-ORDR workshop report. Am J Respir Crit Care Med. 2010;182(12):1554–1562. doi:10.1164/rccm.201006-0869WS
   PubMed Web of Science ®Google Scholar
• Pereira NL, Weinshilboum RM. Cardiovascular pharmacogenomics and individualized drug therapy. Nat Rev Cardiol. 2009;6(10):632–638. doi:10.1038/nrcardio.2009.154
   PubMed Web of Science ®Google Scholar
• Coons JC, Crisamore K, Adams S, et al. A pilot study of oral treprostinil pharmacogenomics and treatment persistence in patients with pulmonary arterial hypertension. Ther Adv Respir Dis. 2021;15:17534666211013688. doi:10.1177/17534666211013688
   Web of Science ®Google Scholar
• Thomeas-McEwing V, Psotka MA, Gamazon ER, et al. Two polymorphic gene loci associated with treprostinil dose in pulmonary arterial hypertension. Pharmacogenet Genomics. 2022;32(4):144–151. doi:10.1097/FPC.0000000000000463
   PubMed Web of Science ®Google Scholar
• Benza RL, Gomberg-Maitland M, Demarco T, et al. Endothelin-1 pathway polymorphisms and outcomes in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2015;192(11):1345–1354. doi:10.1164/rccm.201501-0196OC
   PubMed Web of Science ®Google Scholar
• Markova SM, De Marco T, Bendjilali N, et al. Association of CYP2C9*2 with bosentan-induced liver injury. Clin Pharmacol Ther. 2013;94(6):678–686. doi:10.1038/clpt.2013.143
   PubMed Web of Science ®Google Scholar
• Seyfarth HJ, Favreau N, Tennert C, et al. Genetic susceptibility to hepatoxicity due to bosentan treatment in pulmonary hypertension. Ann Hepatol. 2014;13(6):803–809. doi:10.1016/S1665-2681(19)30983-4
   PubMed Web of Science ®Google Scholar
• Lee CR, Goldstein JA, Pieper JA. Cytochrome P450 2C9 polymorphisms: a comprehensive review of the in-vitro and human data. Pharmacogenetics. 2002;12(3):251–263. doi:10.1097/00008571-200204000-00010
   PubMedGoogle Scholar
• Karnes JH, Rettie AE, Somogyi AA, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and HLA-B Genotypes and Phenytoin Dosing: 2020 Update. Clin Pharmacol Ther. 2021;109(2):302–309. doi:10.1002/cpt.2008
   PubMed Web of Science ®Google Scholar
• Belleville-Rolland T, Sassi Y, Decouture B, et al. MRP4 (ABCC4) as a potential pharmacologic target for cardiovascular disease. Pharmacol Res. 2016;107:381–389. doi:10.1016/j.phrs.2016.04.002
   PubMed Web of Science ®Google Scholar
• Chakinala MM, Feldman JP, Rischard F, et al. Transition from parenteral to oral treprostinil in pulmonary arterial hypertension. J Heart Lung Transplant. 2017;36(2):193–201. doi:10.1016/j.healun.2016.06.019
   PubMed Web of Science ®Google Scholar
• Tapson VF, Torres F, Kermeen F, et al. Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and/or phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C study): a randomized controlled trial. Chest. 2012;142(6):1383–1390. doi:10.1378/chest.11-2212
   PubMed Web of Science ®Google Scholar
• Tapson VF, Jing ZC, Xu KF, et al. Oral treprostinil for the treatment of pulmonary arterial hypertension in patients receiving background endothelin receptor antagonist and phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C2 study): a randomized controlled trial. Chest. 2013;144(3):952–958. doi:10.1378/chest.12-2875
   PubMed Web of Science ®Google Scholar
• White RJ, Jerjes-Sanchez C, Bohns Meyer GM, et al. Combination therapy with oral treprostinil for pulmonary arterial hypertension. A double-blind placebo-controlled clinical trial. Am J Respir Crit Care Med. 2020;201(6):707–717. doi:10.1164/rccm.201908-1640OC
   PubMed Web of Science ®Google Scholar
• Chin KM, Ruggiero R, Bartolome S, et al. Long-term therapy with oral treprostinil in pulmonary arterial hypertension failed to lead to improvement in important physiologic measures: results from a single center. Pulm Circ. 2015;5(3):513–520. doi:10.1086/682224
   PubMed Web of Science ®Google Scholar
• Coons JC, Miller T. Extended-release oral treprostinil in the management of pulmonary arterial hypertension: clinical evidence and experience. Ther Adv Respir Dis. 2018;12:1753466618766490. doi:10.1177/1753466618766490
   Web of Science ®Google Scholar
• Ramani G, Cassady S, Shen E, et al. Novel dose-response analyses of treprostinil in pulmonary arterial hypertension and its effects on six-minute walk distance and hospitalizations. Pulm Circ. 2020;10(3):2045894020923956. doi:10.1177/2045894020923956
   Web of Science ®Google Scholar
• Karczewski KJ, Francioli LC, Tiao G, et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 2020;581(7809):434–443. doi:10.1038/s41586-020-2308-7
   PubMed Web of Science ®Google Scholar
• Yasar U, Lundgren S, Eliasson E, et al. Linkage between the CYP2C8 and CYP2C9 genetic polymorphisms. Biochem Biophys Res Commun. 2002;299(1):25–28. doi:10.1016/S0006-291X(02)02592-5
   PubMed Web of Science ®Google Scholar
• Giaid A, Yanagisawa M, Langleben D, et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med. 1993;328(24):1732–1739. doi:10.1056/NEJM199306173282402
   PubMed Web of Science ®Google Scholar
• Pulido T, Adzerikho I, Channick RN, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369(9):809–818. doi:10.1056/NEJMoa1213917
   PubMed Web of Science ®Google Scholar
• Sitbon O, Badesch DB, Channick RN, et al. Effects of the dual endothelin receptor antagonist bosentan in patients with pulmonary arterial hypertension: a 1-year follow-up study. Chest. 2003;124(1):247–254. doi:10.1378/chest.124.1.247
   PubMed Web of Science ®Google Scholar
• Polderman KH, Stehouwer CD, van Kamp GJ, Dekker GA, Verheugt FW, Gooren LJ. Influence of sex hormones on plasma endothelin levels. Ann Intern Med. 1993;118(6):429–432. doi:10.7326/0003-4819-118-6-199303150-00006
   PubMed Web of Science ®Google Scholar
• Campia U, Cardillo C, Panza JA. Ethnic differences in the vasoconstrictor activity of endogenous endothelin-1 in hypertensive patients. Circulation. 2004;109(25):3191–3195. doi:10.1161/01.CIR.0000130590.24107.D3
   PubMed Web of Science ®Google Scholar
• Gabler NB, French B, Strom BL, et al. Race and sex differences in response to endothelin receptor antagonists for pulmonary arterial hypertension. Chest. 2012;141(1):20–26. doi:10.1378/chest.11-0404
   PubMed Web of Science ®Google Scholar
• Sandoval J, Torbicki A, Souza R, et al. Safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension. Pulm Pharmacol Ther. 2012;25(1):33–39. doi:10.1016/j.pupt.2011.10.002
   PubMed Web of Science ®Google Scholar
• Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002;346(12):896–903. doi:10.1056/NEJMoa012212
   PubMed Web of Science ®Google Scholar
• Denton CP, Pope JE, Peter HH, et al. Long-term effects of bosentan on quality of life, survival, safety and tolerability in pulmonary arterial hypertension related to connective tissue diseases. Ann Rheum Dis. 2008;67(9):1222–1228. doi:10.1136/ard.2007.079921
   PubMed Web of Science ®Google Scholar
• Treiber A, Schneiter R, Hausler S, Stieger B. Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil. Drug Metab Dispos. 2007;35(8):1400–1407. doi:10.1124/dmd.106.013615
   PubMed Web of Science ®Google Scholar
• Burgess G, Hoogkamer H, Collings L, Dingemanse J. Mutual pharmacokinetic interactions between steady-state bosentan and sildenafil. Eur J Clin Pharmacol. 2008;64(1):43–50. doi:10.1007/s00228-007-0408-z
   PubMed Web of Science ®Google Scholar
• van Giersbergen PL, Halabi A, Dingemanse J. Single- and multiple-dose pharmacokinetics of bosentan and its interaction with ketoconazole. Br J Clin Pharmacol. 2002;53(6):589–595. doi:10.1046/j.1365-2125.2002.01608.x
   PubMed Web of Science ®Google Scholar
• Fouassier L, Kinnman N, Lefevre G, et al. Contribution of mrp2 in alterations of canalicular bile formation by the endothelin antagonist bosentan. J Hepatol. 2002;37(2):184–191. doi:10.1016/S0168-8278(02)00107-1
   PubMed Web of Science ®Google Scholar
• Fattinger K, Funk C, Pantze M, et al. The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions. Clin Pharmacol Ther. 2001;69(4):223–231. doi:10.1067/mcp.2001.114667
   PubMed Web of Science ®Google Scholar
• Mano Y, Usui T, Kamimura H. Effects of bosentan, an endothelin receptor antagonist, on bile salt export pump and multidrug resistance-associated protein 2. Biopharm Drug Dispos. 2007;28(1):13–18. doi:10.1002/bdd.527
   PubMed Web of Science ®Google Scholar
• Kirchheiner J, Brockmoller J. Clinical consequences of cytochrome P450 2C9 polymorphisms. Clin Pharmacol Ther. 2005;77(1):1–16. doi:10.1016/j.clpt.2004.08.009
   PubMed Web of Science ®Google Scholar
• Humbert M, Sitbon O, Chaouat A, et al. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation. 2010;122(2):156–163. doi:10.1161/CIRCULATIONAHA.109.911818
   PubMed Web of Science ®Google Scholar
• Benza RL, Gomberg-Maitland M, Elliott CG, et al. Predicting survival in patients with pulmonary arterial hypertension: the REVEAL risk score calculator 2.0 and Comparison With ESC/ERS-based risk assessment strategies. Chest. 2019;156(2):323–337.
   PubMed Web of Science ®Google Scholar
• Peacock AJ, Naeije R, Galie N, Rubin L. End-points and clinical trial design in pulmonary arterial hypertension: have we made progress? Eur Respir J. 2009;34(1):231–242. doi:10.1183/09031936.00107108
   PubMed Web of Science ®Google Scholar
• Said SI, Hamidi SA. Pharmacogenomics in pulmonary arterial hypertension: toward a mechanistic, target-based approach to therapy. Pulm Circ. 2011;1(3):383–388. doi:10.4103/2045-8932.87306
   PubMedGoogle Scholar
• Manolio TA, Collins FS, Cox NJ, et al. Finding the missing heritability of complex diseases. Nature. 2009;461(7265):747–753. doi:10.1038/nature08494
   PubMed Web of Science ®Google Scholar
• Zhong WP, Wu H, Chen JY, et al. Genomewide association study identifies novel genetic loci that modify antiplatelet effects and pharmacokinetics of clopidogrel. Clin Pharmacol Ther. 2017;101(6):791–802. doi:10.1002/cpt.589
   PubMed Web of Science ®Google Scholar
• Gamazon ER, Segre AV, van de Bunt M, et al. Using an atlas of gene regulation across 44 human tissues to inform complex disease- and trait-associated variation. Nat Genet. 2018;50(7):956–967. doi:10.1038/s41588-018-0154-4
   PubMed Web of Science ®Google Scholar
• Maitland ML, Ratain MJ, Cox NJ. Interpreting P values in pharmacogenetic studies: a call for process and perspective. J Clin Oncol. 2007;25(29):4513–4515. doi:10.1200/JCO.2007.12.7803
   PubMed Web of Science ®Google Scholar
• Wheeler HE, Maitland ML, Dolan ME, Cox NJ, Ratain MJ. Cancer pharmacogenomics: strategies and challenges. Nat Rev Genet. 2013;14(1):23–34. doi:10.1038/nrg3352
   PubMed Web of Science ®Google Scholar
• Jones TS, Yang W, Evans WE, Relling MV. Using HapMap tools in pharmacogenomic discovery: the thiopurine methyltransferase polymorphism. Clin Pharmacol Ther. 2007;81(5):729–734. doi:10.1038/sj.clpt.6100135
   PubMed Web of Science ®Google Scholar
• Maranville JC, Cox NJ. Pharmacogenomic variants have larger effect sizes than genetic variants associated with other dichotomous complex traits. Pharmacogenomics J. 2016;16(4):388–392. doi:10.1038/tpj.2015.47
   PubMed Web of Science ®Google Scholar
• Motsinger-Reif AA, Jorgenson E, Relling MV, et al. Genome-wide association studies in pharmacogenomics: successes and lessons. Pharmacogenet Genomics. 2013;23(8):383–394. doi:10.1097/FPC.0b013e32833d7b45
   PubMed Web of Science ®Google Scholar