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Генетический полиморфизм b2-адренорецепторов, сердечно-сосудистые заболевания и влияние на эффективность b-адреноблокаторов
Леонова М.В. Генетический полиморфизм b2-адренорецепторов, сердечно-сосудистые заболевания и влияние на эффективность b-адреноблокаторов. Consilium Medicum. 2020; 22 (5): 92–97. DOI: 10.26442/20751753.2020.5.200107
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Leonova M.V. b2-Adrenergic receptors genetic polymorphism, cardiovascular disorders and influence of b-blockers’ effectiveness. Consilium Medicum. 2020; 22 (5): 92–97. DOI: 10.26442/20751753.2020.5.200107
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Аннотация
Представлен научный обзор данных клинико-генетических исследований о роли полиморфизма b2-адренорецепторов в развитии и исходах сердечно-сосудистых заболеваний. Наибольшее значение в генетическом полиморфизме b2-адренорецепторов имеют три локуса – Arg16Gly, Gln27Glu и Thr164Ile. Вариантные аллели Gly16 и Glu27 изменяют степень подавления (down-регуляция) экспрессии рецептора на фоне стимуляции агонистом, что влияет и на ответ применения b-адреноблокаторов. Вариантный аллель Ile164 встречается крайне редко и приводит к снижению функциональной активности рецептора. Сосудистые эффекты у носителей аллелей Arg16 и Gln27 проявляются более низким исходным кровотоком и значительно ослабленной агонист-стимулированной вазодилатацией в сравнении с носителями вариантных аллелей Gly16 и Glu27. Однако их роль в развитии артериальной гипертонии не получила подтверждения. Полиморфизм b2-адренорецепторов показал наибольшую значимость по влиянию на сердечную функцию, развитие неблагоприятных исходов и выживаемость при хронической сердечной недостаточности, остром коронарном синдроме и других сердечно-сосудистых заболеваниях.
Ключевые слова: генетический полиморфизм, b2-адренорецепторы, b-адреноблокаторы, сердечно-сосудистые исходы, артериальная гипертония, сердечная недостаточность.
Ключевые слова: генетический полиморфизм, b2-адренорецепторы, b-адреноблокаторы, сердечно-сосудистые исходы, артериальная гипертония, сердечная недостаточность.
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A scientific review of clinical and genetic research data on the role of b2-adrenergic receptor polymorphism in the development and outcomes of cardiovascular diseases is presented. Of the greatest importance in the genetic polymorphism of b2-adrenergic receptors are three loci – Arg16Gly, Gln27Glu and Thr164Ile. Variant alleles Gly16 and Glu27 alter the degree of suppression (down-regulation) of receptor expression against the background of agonist stimulation, which also affects the response of b-blockers. The variant allele Ile164 is extremely rare and leads to a decrease in the functional activity of the receptor. Vascular effects in carriers of the Arg16 and Gln27 alleles are manifested by lower initial blood flow and significantly weakened agonist-stimulated vasodilation compared to carriers of variant alleles Gly16 and Glu27. However, their role in the development of arterial hypertension has not been confirmed. Polymorphism of b2-adrenergic receptors showed the greatest significance in terms of its effect on cardiac function, the development of adverse outcomes and survival in chronic heart failure, acute coronary syndrome and other cardiovascular diseases.
Key words: genetic polymorphism, b2-adrenergic receptors, b-blockers, cardiovascular outcomes, arterial hypertension, heart failure.
Полный текст
Список литературы
1. Levin MC, Marullo S, Muntaner O et al. The myocardium-protective Gly-49 variant of the beta 1-adrenergic receptor exhibits constitutive activity and increased desensitization and down-regulation. J Biol Chem 2002; 277: 30429–35. DOI: 10.1074/jbc.M200681200
2. Brodde OE. Beta1- and beta2-adrenoceptor polymorphisms and cardiovascular diseases. Fundam Clin Pharmacol 2008; 22 (2): 107–25. DOI: 10.1111/j.1472-8206.2007.00557.x
3. Green SA, Turki J, Innis M, Liggett SB. Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry 1994; 33: 9414–9. DOI: 10.1021/bi00198a006
4. Liggett SB. Molecular and genetic basis of beta2-adrenergic receptor function. J Allergy Clin Immunol 1999; 104 (2 Pt 2): S42-6. DOI: 10.1016/s0091-6749(99)70272-1
5. Drysdale CM, McGraw DW, Stack CB et al. Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. Proc Natl Acad Sci USA 2000; 97 (19): 10483–8.
DOI: 10.1073/pnas.97.19.10483
6. Leineweber K, Heusch G. b1- and b2-Adrenoceptor polymorphisms and cardiovascular diseases. Br J Pharmacol 2009; 158: 61–9. DOI: 10.1111/j.1476-5381.2009.00187.x
7. Litonjua AA, Gong L, Duan QL et al. Very important pharmacogene summary ADRB2. Pharmacogenetics and genomics 2010; 20 (1): 64–9. DOI: 10.1097/FPC.0b013e328333dae6
8. Cockcroft JR, Gazis AG, Cross DJ et al. Beta(2)-adrenoceptor polymorphism determines vascular reactivity in humans. Hypertension 2000; 36 (3): 371–5. DOI: 10.1161/01.hyp.36.3.371
9. Bruck H, Leineweber K, Büscher R et al. The Gln27Glu beta2-adrenoceptor polymorphism slows the onset of desensitization of cardiac functional responses in vivo. Pharmacogenetics 2003; 13 (2): 59–66. DOI: 10.1097/00008571-200302000-00001
10. Hahntow IN, Koopmans RP, Michel MC. The b2-adrenoceptor gene and hypertension: is it the promoter or the coding region or neither? J Hypertens 2006; 24: 1003–7. DOI: 10.1097/01.hjh.0000226185.06063.80
11. Kitsios GD, Zintzaras E. Synopsis and data synthesis of genetic association studies in hypertension for the adrenergic receptors family genes: the CUMAGAS-HYPERT database. Am J Hypertens 2010; 23 (3): 305–13. DOI: 10.1038/ajh.2009.251
12. Brodde OE. Beta-1 and beta-2 adrenoceptor polymorphisms: functional importance, impact on cardiovascular diseases and drug responses. Pharmacol Ther 2008; 117 (1): 1–29. DOI: 10.1016/j.pharmthera.2007.07.002
13. Binder A, Garcia E, Wallace C et al. Haplotypes of the beta-2 adrenergic receptor associate with high diastolic blood pressure in the Caerphilly prospective study. J Hypertens 2006; 24 (3): 471–7. DOI: 10.1097/01.hjh.0000209983.28735.33
14. Wallerstedt SM, Eriksson AL, Ohlsson C, Hedner T. Haplotype association analysis of the polymorphisms Arg16Gly and Gln27Glu of the adrenergic beta2 receptor in a Swedish hypertensive population. J Hum Hypertens 2005; 19 (9): 705–8.
DOI: 10.1038/sj.jhh.1001897
15. Ge D, Huang J, He J et al. Вeta2-Adrenergic receptor gene variations associated with stage-2 hypertension in northern Han Chinese. Ann Hum Genet 2005; 69 (1): 36–44. DOI: 10.1046/j.1529-8817.2003.00093.x
16. Tang W, Devereux RB, Kitzman DW et al. The Arg16Gly polymorphism of the beta2-adrenergic receptor and left ventricular systolic function. Am J Hypertens 2003; 16 (11 Pt 1): 945–51. DOI: 10.1016/s0895-7061(03)01001-x
17. Snyder EM, Hulsebus ML, Turner ST et al. Genotype related differences in beta2 adrenergic receptor density and cardiac function. Med Sci Sports Exerc 2006; 38 (5): 882–6. DOI: 10.1249/01.mss.0000218144.02831.f6
18. Wolk R, Snyder EM, Somers VK et al. Arginine 16 glycine beta2-adrenoceptor polymorphism and cardiovascular structure and function in patients with heart failure. J Am Soc Echocardiogr 2007; 20 (3): 290–7. DOI: 10.1016/j.echo.2006.08.011
19. Covolo L, Gelatti U, Metra M et al. Role of beta1- and beta2-adrenoceptor polymorphisms in heart failure: a case-control study. Eur Heart J 2004; 25 (17): 1534–41. DOI: 10.1016/j.ehj.2004.06.015
20. Kaye DM, Smirk B, Williams C et al. β-Adrenoceptor genotype influences the response to carvedilol in patients with congestive heart failure. Pharmacogenetics 2003; 13: 379–82. DOI: 10.1097/00008571-200307000-00002
21. Metra M, Covolo L, Pezzali N et al. Role of beta-adrenergic receptor gene polymorphisms in the long-term effects of beta-blockade with carvedilol in patients with chronic heart failure. Cardiovasc Drugs Ther 2010; 24 (1): 49–60. DOI: 10.1007/s10557-010-6220-5
22. Troncoso R, Moraga F, Chiong M et al. Gln(27)→Glu beta(2)-adrenergic receptor polymorphism in heart failure patients: differential clinical and oxidative response to carvedilol. Basic Clin Pharmacol Toxicol 2009; 104 (5): 374–8. DOI: 10.1111/j.1742-7843.2008.00370.x
23. Liggett SB, Wagoner LE, Craft LL et al. The Ile164 beta2-adrenergic receptor polymorphism adversely affects the outcome of congestive heart failure. J Clin Invest 1998; 102: 1534–9. DOI: 10.1172/JCI4059
24. De Groote P, Lamblin N, Helbecque N et al. The impact of beta-adrenoreceptor gene polymorphisms on survival in patients with congestive heart failure. Eur J Heart Fail 2005; 7: 966–73. DOI: 10.1016/j.ejheart.2004.10.006
25. Shin J, Lobmeyer MT, Gong Y et al. Relation of b2-adrenoceptor haplotype to risk of death and heart transplantation in patients with heart failure. Am J Cardiol 2007; 99: 250–5. DOI: 10.1016/j.amjcard.2006.08.020
26. Mansur AJ, Fontes RS, Canzi RA et al. Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly in patients with heart failure. BMC Cardiovasc Disord 2009; 9: 50. DOI: 10.1186/1471-2261-9-50.
27. Huang J, Li C, Song Y et al. ADRB2 polymorphism Arg16Gly modifies the natural outcome of heart failure and dictates therapeutic response to b-blockers in patients with heart failure. Cell Discovery 2018; 4: 57–60. DOI: 10.1038/s41421-018-0058-6
28. Lanfear DE, Jones PG, Marsh S et al. b2-Adrenergic receptor genotype and survival among patients receiving b-blocker therapy after an acute coronary syndrome. JAMA 2005; 294 (12): 1526–33. DOI: 10.1001/jama.294.12.1526
29. Cresci S, Dorn GW, Jones PG et al. Adrenergic-pathway gene variants influence beta-blocker-related outcomes after acute coronary syndrome in a race-specific manner. J Am Coll Cardiol 2012; 60 (10): 898–907. DOI: 10.1016/j.jacc.2012.02.051
30. Heckbert SR, Hindorff LA, Edwards KL et al. Beta2-adrenergic receptor polymorphisms and risk of incident cardiovascular events in the elderly. Circulation 2003; 107 (15): 2021–4. DOI: 10.1161/01.CIR.0000065231.07729.92
31. Sotoodehnia N, Siscovick DS, Vatta M et al. b2-Adrenergic receptor genetic variants and risk of sudden cardiac death. Circulation 2006; 113: 1842–8. DOI: 10.1161/CIRCULATIONAHA.105.582833
2. Brodde OE. Beta1- and beta2-adrenoceptor polymorphisms and cardiovascular diseases. Fundam Clin Pharmacol 2008; 22 (2): 107–25. DOI: 10.1111/j.1472-8206.2007.00557.x
3. Green SA, Turki J, Innis M, Liggett SB. Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry 1994; 33: 9414–9. DOI: 10.1021/bi00198a006
4. Liggett SB. Molecular and genetic basis of beta2-adrenergic receptor function. J Allergy Clin Immunol 1999; 104 (2 Pt 2): S42-6. DOI: 10.1016/s0091-6749(99)70272-1
5. Drysdale CM, McGraw DW, Stack CB et al. Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. Proc Natl Acad Sci USA 2000; 97 (19): 10483–8.
DOI: 10.1073/pnas.97.19.10483
6. Leineweber K, Heusch G. b1- and b2-Adrenoceptor polymorphisms and cardiovascular diseases. Br J Pharmacol 2009; 158: 61–9. DOI: 10.1111/j.1476-5381.2009.00187.x
7. Litonjua AA, Gong L, Duan QL et al. Very important pharmacogene summary ADRB2. Pharmacogenetics and genomics 2010; 20 (1): 64–9. DOI: 10.1097/FPC.0b013e328333dae6
8. Cockcroft JR, Gazis AG, Cross DJ et al. Beta(2)-adrenoceptor polymorphism determines vascular reactivity in humans. Hypertension 2000; 36 (3): 371–5. DOI: 10.1161/01.hyp.36.3.371
9. Bruck H, Leineweber K, Büscher R et al. The Gln27Glu beta2-adrenoceptor polymorphism slows the onset of desensitization of cardiac functional responses in vivo. Pharmacogenetics 2003; 13 (2): 59–66. DOI: 10.1097/00008571-200302000-00001
10. Hahntow IN, Koopmans RP, Michel MC. The b2-adrenoceptor gene and hypertension: is it the promoter or the coding region or neither? J Hypertens 2006; 24: 1003–7. DOI: 10.1097/01.hjh.0000226185.06063.80
11. Kitsios GD, Zintzaras E. Synopsis and data synthesis of genetic association studies in hypertension for the adrenergic receptors family genes: the CUMAGAS-HYPERT database. Am J Hypertens 2010; 23 (3): 305–13. DOI: 10.1038/ajh.2009.251
12. Brodde OE. Beta-1 and beta-2 adrenoceptor polymorphisms: functional importance, impact on cardiovascular diseases and drug responses. Pharmacol Ther 2008; 117 (1): 1–29. DOI: 10.1016/j.pharmthera.2007.07.002
13. Binder A, Garcia E, Wallace C et al. Haplotypes of the beta-2 adrenergic receptor associate with high diastolic blood pressure in the Caerphilly prospective study. J Hypertens 2006; 24 (3): 471–7. DOI: 10.1097/01.hjh.0000209983.28735.33
14. Wallerstedt SM, Eriksson AL, Ohlsson C, Hedner T. Haplotype association analysis of the polymorphisms Arg16Gly and Gln27Glu of the adrenergic beta2 receptor in a Swedish hypertensive population. J Hum Hypertens 2005; 19 (9): 705–8.
DOI: 10.1038/sj.jhh.1001897
15. Ge D, Huang J, He J et al. Вeta2-Adrenergic receptor gene variations associated with stage-2 hypertension in northern Han Chinese. Ann Hum Genet 2005; 69 (1): 36–44. DOI: 10.1046/j.1529-8817.2003.00093.x
16. Tang W, Devereux RB, Kitzman DW et al. The Arg16Gly polymorphism of the beta2-adrenergic receptor and left ventricular systolic function. Am J Hypertens 2003; 16 (11 Pt 1): 945–51. DOI: 10.1016/s0895-7061(03)01001-x
17. Snyder EM, Hulsebus ML, Turner ST et al. Genotype related differences in beta2 adrenergic receptor density and cardiac function. Med Sci Sports Exerc 2006; 38 (5): 882–6. DOI: 10.1249/01.mss.0000218144.02831.f6
18. Wolk R, Snyder EM, Somers VK et al. Arginine 16 glycine beta2-adrenoceptor polymorphism and cardiovascular structure and function in patients with heart failure. J Am Soc Echocardiogr 2007; 20 (3): 290–7. DOI: 10.1016/j.echo.2006.08.011
19. Covolo L, Gelatti U, Metra M et al. Role of beta1- and beta2-adrenoceptor polymorphisms in heart failure: a case-control study. Eur Heart J 2004; 25 (17): 1534–41. DOI: 10.1016/j.ehj.2004.06.015
20. Kaye DM, Smirk B, Williams C et al. β-Adrenoceptor genotype influences the response to carvedilol in patients with congestive heart failure. Pharmacogenetics 2003; 13: 379–82. DOI: 10.1097/00008571-200307000-00002
21. Metra M, Covolo L, Pezzali N et al. Role of beta-adrenergic receptor gene polymorphisms in the long-term effects of beta-blockade with carvedilol in patients with chronic heart failure. Cardiovasc Drugs Ther 2010; 24 (1): 49–60. DOI: 10.1007/s10557-010-6220-5
22. Troncoso R, Moraga F, Chiong M et al. Gln(27)→Glu beta(2)-adrenergic receptor polymorphism in heart failure patients: differential clinical and oxidative response to carvedilol. Basic Clin Pharmacol Toxicol 2009; 104 (5): 374–8. DOI: 10.1111/j.1742-7843.2008.00370.x
23. Liggett SB, Wagoner LE, Craft LL et al. The Ile164 beta2-adrenergic receptor polymorphism adversely affects the outcome of congestive heart failure. J Clin Invest 1998; 102: 1534–9. DOI: 10.1172/JCI4059
24. De Groote P, Lamblin N, Helbecque N et al. The impact of beta-adrenoreceptor gene polymorphisms on survival in patients with congestive heart failure. Eur J Heart Fail 2005; 7: 966–73. DOI: 10.1016/j.ejheart.2004.10.006
25. Shin J, Lobmeyer MT, Gong Y et al. Relation of b2-adrenoceptor haplotype to risk of death and heart transplantation in patients with heart failure. Am J Cardiol 2007; 99: 250–5. DOI: 10.1016/j.amjcard.2006.08.020
26. Mansur AJ, Fontes RS, Canzi RA et al. Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly in patients with heart failure. BMC Cardiovasc Disord 2009; 9: 50. DOI: 10.1186/1471-2261-9-50.
27. Huang J, Li C, Song Y et al. ADRB2 polymorphism Arg16Gly modifies the natural outcome of heart failure and dictates therapeutic response to b-blockers in patients with heart failure. Cell Discovery 2018; 4: 57–60. DOI: 10.1038/s41421-018-0058-6
28. Lanfear DE, Jones PG, Marsh S et al. b2-Adrenergic receptor genotype and survival among patients receiving b-blocker therapy after an acute coronary syndrome. JAMA 2005; 294 (12): 1526–33. DOI: 10.1001/jama.294.12.1526
29. Cresci S, Dorn GW, Jones PG et al. Adrenergic-pathway gene variants influence beta-blocker-related outcomes after acute coronary syndrome in a race-specific manner. J Am Coll Cardiol 2012; 60 (10): 898–907. DOI: 10.1016/j.jacc.2012.02.051
30. Heckbert SR, Hindorff LA, Edwards KL et al. Beta2-adrenergic receptor polymorphisms and risk of incident cardiovascular events in the elderly. Circulation 2003; 107 (15): 2021–4. DOI: 10.1161/01.CIR.0000065231.07729.92
31. Sotoodehnia N, Siscovick DS, Vatta M et al. b2-Adrenergic receptor genetic variants and risk of sudden cardiac death. Circulation 2006; 113: 1842–8. DOI: 10.1161/CIRCULATIONAHA.105.582833
________________________________________________
1. Levin MC, Marullo S, Muntaner O et al. The myocardium-protective Gly-49 variant of the beta 1-adrenergic receptor exhibits constitutive activity and increased desensitization and down-regulation. J Biol Chem 2002; 277: 30429–35. DOI: 10.1074/jbc.M200681200
2. Brodde OE. Beta1- and beta2-adrenoceptor polymorphisms and cardiovascular diseases. Fundam Clin Pharmacol 2008; 22 (2): 107–25. DOI: 10.1111/j.1472-8206.2007.00557.x
3. Green SA, Turki J, Innis M, Liggett SB. Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry 1994; 33: 9414–9. DOI: 10.1021/bi00198a006
4. Liggett SB. Molecular and genetic basis of beta2-adrenergic receptor function. J Allergy Clin Immunol 1999; 104 (2 Pt 2): S42-6. DOI: 10.1016/s0091-6749(99)70272-1
5. Drysdale CM, McGraw DW, Stack CB et al. Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. Proc Natl Acad Sci USA 2000; 97 (19): 10483–8. DOI: 10.1073/pnas.97.19.10483
6. Leineweber K, Heusch G. b1- and b2-Adrenoceptor polymorphisms and cardiovascular diseases. Br J Pharmacol 2009; 158: 61–9. DOI: 10.1111/j.1476-5381.2009.00187.x
7. Litonjua AA, Gong L, Duan QL et al. Very important pharmacogene summary ADRB2. Pharmacogenetics and genomics 2010; 20 (1): 64–9.
DOI: 10.1097/FPC.0b013e328333dae6
8. Cockcroft JR, Gazis AG, Cross DJ et al. Beta(2)-adrenoceptor polymorphism determines vascular reactivity in humans. Hypertension 2000; 36 (3): 371–5. DOI: 10.1161/01.hyp.36.3.371
9. Bruck H, Leineweber K, Büscher R et al. The Gln27Glu beta2-adrenoceptor polymorphism slows the onset of desensitization of cardiac functional responses in vivo. Pharmacogenetics 2003; 13 (2): 59–66. DOI: 10.1097/00008571-200302000-00001
10. Hahntow IN, Koopmans RP, Michel MC. The b2-adrenoceptor gene and hypertension: is it the promoter or the coding region or neither? J Hypertens 2006; 24: 1003–7. DOI: 10.1097/01.hjh.0000226185.06063.80
11. Kitsios GD, Zintzaras E. Synopsis and data synthesis of genetic association studies in hypertension for the adrenergic receptors family genes: the CUMAGAS-HYPERT database. Am J Hypertens 2010; 23 (3): 305–13. DOI: 10.1038/ajh.2009.251
12. Brodde OE. Beta-1 and beta-2 adrenoceptor polymorphisms: functional importance, impact on cardiovascular diseases and drug responses. Pharmacol Ther 2008; 117 (1): 1–29. DOI: 10.1016/j.pharmthera.2007.07.002
13. Binder A, Garcia E, Wallace C et al. Haplotypes of the beta-2 adrenergic receptor associate with high diastolic blood pressure in the Caerphilly prospective study. J Hypertens 2006; 24 (3): 471–7. DOI: 10.1097/01.hjh.0000209983.28735.33
14. Wallerstedt SM, Eriksson AL, Ohlsson C, Hedner T. Haplotype association analysis of the polymorphisms Arg16Gly and Gln27Glu of the adrenergic beta2 receptor in a Swedish hypertensive population. J Hum Hypertens 2005; 19 (9): 705–8. DOI: 10.1038/sj.jhh.1001897
15. Ge D, Huang J, He J et al. Вeta2-Adrenergic receptor gene variations associated with stage-2 hypertension in northern Han Chinese. Ann Hum Genet 2005; 69 (1): 36–44. DOI: 10.1046/j.1529-8817.2003.00093.x
16. Tang W, Devereux RB, Kitzman DW et al. The Arg16Gly polymorphism of the beta2-adrenergic receptor and left ventricular systolic function. Am J Hypertens 2003; 16 (11 Pt 1): 945–51. DOI: 10.1016/s0895-7061(03)01001-x
17. Snyder EM, Hulsebus ML, Turner ST et al. Genotype related differences in beta2 adrenergic receptor density and cardiac function. Med Sci Sports Exerc 2006; 38 (5): 882–6. DOI: 10.1249/01.mss.0000218144.02831.f6
18. Wolk R, Snyder EM, Somers VK et al. Arginine 16 glycine beta2-adrenoceptor polymorphism and cardiovascular structure and function in patients with heart failure. J Am Soc Echocardiogr 2007; 20 (3): 290–7. DOI: 10.1016/j.echo.2006.08.011
19. Covolo L, Gelatti U, Metra M et al. Role of beta1- and beta2-adrenoceptor polymorphisms in heart failure: a case-control study. Eur Heart J 2004; 25 (17): 1534–41. DOI: 10.1016/j.ehj.2004.06.015
20. Kaye DM, Smirk B, Williams C et al. β-Adrenoceptor genotype influences the response to carvedilol in patients with congestive heart failure. Pharmacogenetics 2003; 13: 379–82. DOI: 10.1097/00008571-200307000-00002
21. Metra M, Covolo L, Pezzali N et al. Role of beta-adrenergic receptor gene polymorphisms in the long-term effects of beta-blockade with carvedilol in patients with chronic heart failure. Cardiovasc Drugs Ther 2010; 24 (1): 49–60. DOI: 10.1007/s10557-010-6220-5
22. Troncoso R, Moraga F, Chiong M et al. Gln(27)→Glu beta(2)-adrenergic receptor polymorphism in heart failure patients: differential clinical and oxidative response to carvedilol. Basic Clin Pharmacol Toxicol 2009; 104 (5): 374–8. DOI: 10.1111/j.1742-7843.2008.00370.x
23. Liggett SB, Wagoner LE, Craft LL et al. The Ile164 beta2-adrenergic receptor polymorphism adversely affects the outcome of congestive heart failure. J Clin Invest 1998; 102: 1534–9. DOI: 10.1172/JCI4059
24. De Groote P, Lamblin N, Helbecque N et al. The impact of beta-adrenoreceptor gene polymorphisms on survival in patients with congestive heart failure. Eur J Heart Fail 2005; 7: 966–73. DOI: 10.1016/j.ejheart.2004.10.006
25. Shin J, Lobmeyer MT, Gong Y et al. Relation of b2-adrenoceptor haplotype to risk of death and heart transplantation in patients with heart failure. Am J Cardiol 2007; 99: 250–5. DOI: 10.1016/j.amjcard.2006.08.020
26. Mansur AJ, Fontes RS, Canzi RA et al. Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly in patients with heart failure. BMC Cardiovasc Disord 2009; 9: 50. DOI: 10.1186/1471-2261-9-50.
27. Huang J, Li C, Song Y et al. ADRB2 polymorphism Arg16Gly modifies the natural outcome of heart failure and dictates therapeutic response to b-blockers in patients with heart failure. Cell Discovery 2018; 4: 57–60. DOI: 10.1038/s41421-018-0058-6
28. Lanfear DE, Jones PG, Marsh S et al. b2-Adrenergic receptor genotype and survival among patients receiving b-blocker therapy after an acute coronary syndrome. JAMA 2005; 294 (12): 1526–33. DOI: 10.1001/jama.294.12.1526
29. Cresci S, Dorn GW, Jones PG et al. Adrenergic-pathway gene variants influence beta-blocker-related outcomes after acute coronary syndrome in a race-specific manner. J Am Coll Cardiol 2012; 60 (10): 898–907. DOI: 10.1016/j.jacc.2012.02.051
30. Heckbert SR, Hindorff LA, Edwards KL et al. Beta2-adrenergic receptor polymorphisms and risk of incident cardiovascular events in the elderly. Circulation 2003; 107 (15): 2021–4. DOI: 10.1161/01.CIR.0000065231.07729.92
31. Sotoodehnia N, Siscovick DS, Vatta M et al. b2-Adrenergic receptor genetic variants and risk of sudden cardiac death. Circulation 2006; 113: 1842–8. DOI: 10.1161/CIRCULATIONAHA.105.582833
Авторы
М.В. Леонова*
Межрегиональная общественная организация «Ассоциация клинических фармакологов», Волгоград, Россия
*anti23@mail.ru
Межрегиональная общественная организация «Ассоциация клинических фармакологов», Волгоград, Россия
*anti23@mail.ru
________________________________________________
Marina V. Leonova*
Association of Clinical Pharmacologists, Volgograd, Russia
*anti23@mail.ru
Цель портала OmniDoctor – предоставление профессиональной информации врачам, провизорам и фармацевтам.