Pulmonary arterial hypertension: Insights from genetic studies

Proceedings of the American Thoracic Society

Volumn 8, Issue 2, 2011, Pages 154-157

  Loyd, James E ^a  

^a VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Pulmonary; Pulmonary artery; Pulmonary hypertension

Indexed keywords

BIOLOGICAL RESPONSE MODIFIER; BONE MORPHOGENETIC PROTEIN RECEPTOR 2; CYTOCHROME P450 1B1; ENDOTHELIN RECEPTOR ANTAGONIST; ESTROGEN; PHOSPHODIESTERASE INHIBITOR; PROSTACYCLIN DERIVATIVE; SMAD8 PROTEIN; TRANSFORMING GROWTH FACTOR BETA1;

ALLELE; CONFERENCE PAPER; DNA MICROARRAY; FAMILIAL DISEASE; GENE EXPRESSION; GENE MUTATION; GENETIC COUNSELING; HEALTH DISPARITY; HEREDITARY HYPERTENSION; HETEROZYGOTE DETECTION; HISTOPATHOLOGY; HUMAN; IDIOPATHIC DISEASE; MISSENSE MUTATION; NONHUMAN; NONSENSE MEDIATED MRNA DECAY; PENETRANCE; PERSONALIZED MEDICINE; PHENOTYPE; PULMONARY HYPERTENSION; RISK; SEX DIFFERENCE; WILD TYPE;

ANIMALS; BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II; DISEASE MODELS, ANIMAL; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GERM-LINE MUTATION; HUMANS; HYPERTENSION, PULMONARY; MALE; MICE; SEX FACTORS;

EID: 80051771345     PISSN: 15463222     EISSN: 19435665     Source Type: Journal    
DOI: 10.1513/pats.201007-047MS     Document Type: Conference Paper

References (26)

1. Rich S, Dantzker DR, Ayres SM, Bergofsky, EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Koerner SK, et al. Primary pulmonary hypertension: a national prospective study. Ann Intern Med 1987;107:216-223. (Pubitemid 17137857)
2. McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol 2009;53:1573-1619.
3. Macchia A, Marchioli R, Marfisi R, Scarano M, Levantesi G, Tavazzi L, Tognoni G. A meta-analysis of trials of pulmonary hypertension: a clinical condition looking for drugs and research methodology. Am Heart J 2007;153:1037-1047. (Pubitemid 46809838)
4. Galie N, Manes A, Negro L, Palazzini M, Bacchi-Reggiani ML, Branzi A. A meta-analysis of randomized controlled trials in pulmonary arterial hypertension. Eur Heart J 2009;30:394-403.
5. Macchia A, Marchioli R, Tognoni G, Scarano M, Marfisi R, Tavazzi L, Rich S. Systematic review of trials using vasodilators in pulmonary arterial hypertension: why a new approach is needed. Am Heart J 2010;159:245-257.
6. Badesch DB, Raskob GE, Elliott CG, Krichman AM, Farber HW, Frost AE, Barst RJ, Benaz RL, Liou TG, Turner M. et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest 2010;137:376-387.
7. Sztrymf B, Coulet F, Girerd B, Yaici A, Jais X, Sitbon O, Montani D, Souza R, Simonneau G, Soubrier F, et al. Clinical outcomes of pulmonary arterial hypertension in carriers of BMPR2 mutation. Am J Respir Crit Care Med 2008;177:1377-1383. (Pubitemid 351860916)
8. Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, Yaici A, Weitzenblum E, Cordier JF, Chabot F, et al. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation 2010;122:156-163.
9. Loyd JE, Primm RK, Newman JH. Familial primary pulmonary hypertension: clinical patterns. Am Rev Respir Dis 1984;129:194-197. (Pubitemid 14176528)
10. Nichols WC, Koller DL, Slovis B, Foroud T, Terry VH, Arnold ND, Siemieniak DR, Wheeler L, Phillips JA, III, Newman JH, et al. Localization of the gene for familial primary pulmonary hypertension to chromosome 2q31-32. Nat Genet 1997;15:277-280. (Pubitemid 27098722)
11. Lane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips JA, III, Loyd JE, Nichols WC, Trembath, RC. Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. The International PPH Consortium. Nat Genet 2000;26:81-84.
12. Morse JH, Jones AC, Barst RJ, Hodge SE, Wilhelmsen KC, Nygaard TG. Mapping of familial primary pulmonary hypertension locus (PPH1) to chromosome 2q31-q32. Circulation 1997;95:2603-2606. (Pubitemid 27255485)
13. Deng Z, Morse JH, Slager SL, Cuervo N, Moore KJ, Ventos G, Kalachikov S, Cayanis E, Fischer SG, Barst RJ, et al. Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. Am J Hum Genet 2000; 67:737-744. (Pubitemid 30659603)
14. Thomson JR, Machado RD, Pauciulo MW, Morgan NV, Humbert M, Elliott GC, Ward K, Yacoub M, Milkhail G, Rogers P, et al. Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGFbeta family. J Med Genet 2000;37:741-745.
15. Grunig E, Koehler R, Miltenberger-Miltenyi G, Zimmermann R, Gorenflo M, Mereles D, Arnold K, Naust B, Wilkens H, Benz A, et al. Primary pulmonary hypertension in children may have a different genetic background than in adults. Pediatr Res 2004;56:571-578.
16. Morisaki H, Nakanishi N, Kyotani S, Takashima A, Tomoike H, Morisaki T. BMPR2 mutations found in Japanese patients with familial and sporadic primary pulmonary hypertension. Hum Mutat 2004;23:632.
17. Cogan JD, Vnencak-Jones CL, Phillips JA, III, Lane KB, Wheeler LA, Robbins IM, Garrison G, Hedges LK, Loyd JE. Gross BMPR2 gene rearrangements constitute a new cause for primary pulmonary hypertension. Genet Med 2005;7:169-174. (Pubitemid 40478153)
18. Trembath RC, Thomson JR, Machado RD, Morgan NV, Atkinson C, Winship I, Simonneau G, Galie N, Loyd JE, Humbert M, et al. Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. N Engl J Med 2001;345:325-334. (Pubitemid 32703235)
19. Phillips JA III, Poling JS, Phillips CA, Stanton KC, Austin ED, Cogan JD, Wheeler L, Yu C, Newman JH, Dietz HC, et al. Synergistic heterozygosity for TGFbeta1 SNPs and BMPR2 mutations modulates the age at diagnosis and penetrance of familial pulmonary arterial hypertension. Genet Med 2008;10:359-365. (Pubitemid 351770407)
20. Austin ED, Phillips JA, III, Cogan JD, Hamid R, Yu C, Stanton KC, Phillips CA, Wheeler LA, Robbins IM, Newman JH, et al. Truncating and missense BMPR2 mutations differentially affect the severity of heritable pulmonary arterial hypertension. Respir Res 2009;10:87.
21. Hamid R, Hedges LK, Austin E, Phillips JA, III, Loyd JE, Cogan JD. Transcripts from a novel BMPR2 termination mutation escape nonsense mediated decay by downstream translation re-initiation: implications for treating pulmonary hypertension. Clin Genet 2010; 77:280-286.
22. Hamid R, Cogan JD, Hedges LK, Austin E, Phillips JA, III, Newman JH, Loyd JE. Penetrance of pulmonary arterial hypertension is modulated by the expression of normal BMPR2 allele. Hum Mutat 2009;30:649-654.
23. West J, Cogan J, Geraci M, Robinson L, Newman J, Phillips JA, Lane K, Meyrick B, Loyd J. Gene expression in BMPR2 mutation carriers with and without evidence of pulmonary arterial hypertension suggests pathways relevant to disease penetrance. BMC Med Genomics 2008;1:45.
24. Austin ED, Cogan JD, West JD, Hedges LK, Hamid R, Dawson EP, Wheeler LA, Parl FF, Loyd JE, Phillips JA, III. Alterations in oestrogen metabolism: implications for higher penetrance of familial pulmonary arterial hypertension in females. Eur Respir J 2009;34: 1093-1099.
25. Rodriguez-Murillo L, Subaran R, Stewart WC, Pramanik S, Marathe S, Barst RJ, Chung WK, Greenberg DA. Novel loci interacting epistatically with bone morphogenetic protein receptor 2 cause familial pulmonary arterial hypertension. J Heart Lung Transplant 2009;29: 174-180.
26. Johnson JA, Hemnes AR, Lane KB, Robinson L, Gladson S, West J. ACE2 reverses established pulmonary arterial hypertension in BMPR2899X mice [abstract]. Am J Respir Crit Care Med 2010;181: A6327.