Влияние генетических маркеров на прогрессирование фибрилляции предсердий у больных с артериальной гипертонией и ожирением
Влияние генетических маркеров на прогрессирование фибрилляции предсердий у больных с артериальной гипертонией и ожирением
Хидирова Л.Д., Яхонтов Д.А., Максимов В.Н. Влияние генетических маркеров на прогрессирование фибрилляции предсердий у больных артериальной гипертонией и ожирением. Терапевтический архив. 2021; 93 (1): 41–43. DOI: 10.26442/00403660.2021.01.200591
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Аннотация
Цель. Изучить значение полиморфизмов rs1378942 гена CSK и rs2200733 (хромосома 4q25) в прогрессировании фибрилляции предсердий (ФП) у мужчин с артериальной гипертонией (АГ) и абдоминальным ожирением (АО).
Материалы и методы. В обсервационном когортном исследовании наблюдались 116 мужчин в возрасте 45–65 лет. Из них 57 пациентов с ФП, АГ и АО и группа контроля в числе 59 пациентов с ФП, АГ и без АО. Тестирование полиморфизма rs1378942 гена CSK и rs2200733 хромосомы 4q25 с помощью полимеразной цепной реакции с полиморфизмом длин рестрикционных фрагментов. Все статистические расчеты проводили в программе Rstudio (version 0.99.879 – ©2009–2016 RStudio, Inc., USA).
Результаты. Средний возраст всех исследуемых пациентов составил 53,3±7,1 года. При разделении пациентов с ФП и АГ на группы по признаку наличия/отсутствия АО оказалось, что в подгруппах носителей разных генотипов полиморфизма rs1378942 гена CSK имеются достоверные различия по индексу массы тела (ИМТ): в группе с нормальным ИМТ наблюдается повышение показателя в ряду генотипов СС, АС, АА. Самое высокое значение ИМТ у носителей генотипа СС (р<0,03) в группе с АО. В подгруппах носителей разных генотипов rs2200733 хромосомы 4q25 – у СС наибольший ИМТ (р<0,05). Доказали, что в группе с АО прогрессирование ФП происходило в 2,57 раза чаще, чем в группе без АО (р<0,003).
Заключение. У мужчин с ФП и АГ однонуклеотидные полиморфизмы rs1378942 гена CSK и rs2200733 хромосомы 4q25 ассоциированы с ИМТ. Гетерозиготный генотип АС rs1378942 в гене CSK достоверно чаще встречается у больных, независимо от наличия АО. В группе с АО прогрессирование ФП происходило в 2,57 раза чаще, чем в группе без АО.
Ключевые слова: фибрилляция предсердий, гипертоническая болезнь, абдоминальное ожирение, полиморфизм, rs1378942, ген, CSK, rs2200733
Materials and methods. In an observational cohort study, 116 men aged 45–65 years were followed. Of these, 57 patients with AF, AH and AO and a control group including 59 patients with AF, AH and without AO. Testing of polymorphism rs1378942 of the CSK gene and rs2200733 of chromosome 4q25 using polymerase chain reaction with restriction fragment length polymorphism. All statistical calculations were performed using the Rstudio program (version 0.99.879 – ©2009–2016 RStudio, Inc., USA).
Results. The average age of all studied patients was 53.3±7.1 years. When dividing patients with AF and AH into groups based on the presence/absence of AO, it turned out that in the subgroups of carriers of different genotypes of the rs1378942 polymorphism of the CSK gene there are significant differences in BMI: in the group with BMI, there is an increase in the indicator in the series of CC, AC, AA genotypes. The highest BMI value in carriers of the CC genotype (p<0.03) was in the group with AO. In the subgroups of carriers of different rs2200733 genotypes of chromosome 4q25, CC has the highest BMI (p<0.05). It was proved that in the group with AO, the progression of AF occurred 2.57 times more often than in the group without AO (p<0.003).
Conclusion. In men with AF and AH, single nucleotide polymorphisms rs1378942 of the CSK gene and rs2200733 of chromosome 4q25 are associated with BMI. The heterozygous genotype AC rs1378942 in the CSK gene is significantly more common in patients, regardless of the presence of AO. In the group with AO, the progression of AF occurred 2.57 times more often than in the group without AO.
Keywords: atrial fibrillation, hypertension, obesity, rs1378942 polymorphism of the CSK gene, rs2200733 chromosome 4q25
Материалы и методы. В обсервационном когортном исследовании наблюдались 116 мужчин в возрасте 45–65 лет. Из них 57 пациентов с ФП, АГ и АО и группа контроля в числе 59 пациентов с ФП, АГ и без АО. Тестирование полиморфизма rs1378942 гена CSK и rs2200733 хромосомы 4q25 с помощью полимеразной цепной реакции с полиморфизмом длин рестрикционных фрагментов. Все статистические расчеты проводили в программе Rstudio (version 0.99.879 – ©2009–2016 RStudio, Inc., USA).
Результаты. Средний возраст всех исследуемых пациентов составил 53,3±7,1 года. При разделении пациентов с ФП и АГ на группы по признаку наличия/отсутствия АО оказалось, что в подгруппах носителей разных генотипов полиморфизма rs1378942 гена CSK имеются достоверные различия по индексу массы тела (ИМТ): в группе с нормальным ИМТ наблюдается повышение показателя в ряду генотипов СС, АС, АА. Самое высокое значение ИМТ у носителей генотипа СС (р<0,03) в группе с АО. В подгруппах носителей разных генотипов rs2200733 хромосомы 4q25 – у СС наибольший ИМТ (р<0,05). Доказали, что в группе с АО прогрессирование ФП происходило в 2,57 раза чаще, чем в группе без АО (р<0,003).
Заключение. У мужчин с ФП и АГ однонуклеотидные полиморфизмы rs1378942 гена CSK и rs2200733 хромосомы 4q25 ассоциированы с ИМТ. Гетерозиготный генотип АС rs1378942 в гене CSK достоверно чаще встречается у больных, независимо от наличия АО. В группе с АО прогрессирование ФП происходило в 2,57 раза чаще, чем в группе без АО.
Ключевые слова: фибрилляция предсердий, гипертоническая болезнь, абдоминальное ожирение, полиморфизм, rs1378942, ген, CSK, rs2200733
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Materials and methods. In an observational cohort study, 116 men aged 45–65 years were followed. Of these, 57 patients with AF, AH and AO and a control group including 59 patients with AF, AH and without AO. Testing of polymorphism rs1378942 of the CSK gene and rs2200733 of chromosome 4q25 using polymerase chain reaction with restriction fragment length polymorphism. All statistical calculations were performed using the Rstudio program (version 0.99.879 – ©2009–2016 RStudio, Inc., USA).
Results. The average age of all studied patients was 53.3±7.1 years. When dividing patients with AF and AH into groups based on the presence/absence of AO, it turned out that in the subgroups of carriers of different genotypes of the rs1378942 polymorphism of the CSK gene there are significant differences in BMI: in the group with BMI, there is an increase in the indicator in the series of CC, AC, AA genotypes. The highest BMI value in carriers of the CC genotype (p<0.03) was in the group with AO. In the subgroups of carriers of different rs2200733 genotypes of chromosome 4q25, CC has the highest BMI (p<0.05). It was proved that in the group with AO, the progression of AF occurred 2.57 times more often than in the group without AO (p<0.003).
Conclusion. In men with AF and AH, single nucleotide polymorphisms rs1378942 of the CSK gene and rs2200733 of chromosome 4q25 are associated with BMI. The heterozygous genotype AC rs1378942 in the CSK gene is significantly more common in patients, regardless of the presence of AO. In the group with AO, the progression of AF occurred 2.57 times more often than in the group without AO.
Keywords: atrial fibrillation, hypertension, obesity, rs1378942 polymorphism of the CSK gene, rs2200733 chromosome 4q25
Список литературы
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10. Jennsen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. JACC. 2014;63(25):2985-3023. Available at: https:www.acc./guidelines. doi: 10.1161/01.cir.0000437739.71477.ee
11. Coutinho T, Goel K, Corrêa de Sá D, et al. Combining Body Mass Index With Measures of Central Obesity in the Assessment of Mortality in Subjects With Coronary Disease: Role of “Normal Weight Central Obesity”. J Am Coll Cardiol. 2013;61(5):553-60. doi: 10.1016/j.jacc.2012.10.035
12. Sandhu RK, Ezekowitz J, Andersson U, et al. The “obesity paradox” in atrial fibrillation: observations from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Eur Heart J. 2016;37:2869-78. doi: 10.1093/eurheartj/ehw124
13. Littleton SW, Mokhlesi B. The pickwickian syndrome-obesity hypoventilation syndrome. Clin Chest Med. 2009; 30(3):467-78. doi: 10.1093/eurheartj/ehw124
14. Guidelines Committee. 2003 European Society of Hypertension-European Society of Cardiology guidelines for management of arterial hypertension. J Hypertens. 2013;21:1011-53. doi: 10.1097/HJH.0000000000000466
15. The Expert Panel. Third Report of the National cholesterol in Educational Program [NCEP] Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults [Adult Treatment Panel III] FinalReport. Circ. 2012;106:3143-421. doi: 10.1016/j.cccn.2004.08.012
16. Zafrir B, Adir Y, Shehadeh W, et al. The association between obesity, mortality and filling pressures in pulmonary hypertension patients; the «obesity paradox». Respir Med. 2013;107(1):139-46. doi: 0.1016/j.rmed.2012.10.019
17. Kirchhof P, Bax J, Blomstrom-Lundquist C, et al. Early and comprehensive management of atrial fibrillation: executive summary of the proceedings from the 2nd AFnEt-EHRA consensus conference ‘research perspectives in AF. Eur Heart J. 2009;30(24):2969-77. doi: 10.1093/eurheartj/ehp235
18. Rai R, Sharma KL, Misra S. CYP17 polymorphism [rs743572] is associated with increased risk of gallbladder cancer in tobacco users. Tumour Biol. 2014;35(7):6531-7. Available at: https:link.springer.com/article/
10.1007%2Fs13277-014-1876-2. doi: 10.1007/s13277-014-1876-2
19. Goodloe AH, Herron KJ, Olson TM. Uncovering an intermediate phenotype associated with rs2200733 at 4q25 in lone atrial fibrillation. Am J Cardiol. 2014;107(12):1802-5. doi: 10.1016%2Fj.amjcard.2013.08.045
2. Клинические рекомендации «Диагностика и лечение фибрилляции предсердий». М., 2017 [Clinical recommendations “Diagnosis and treatment of atrial fibrillation”. Moscow, 2017 (In Russ.)].
3. Thomas F, Bean K, Pannier B, et al. Cardiovascular mortality in overweight subjects. The key role of associated risk factors. Hypertension. 2005;46:654-63. doi: 10.1161/01.HYP.0000184282.51550.00
4. Khidirova LD, Yakhontov DA, Kurope TS, Zenin SA. Atrial fibrillation in combination with arterial hypertension and obesity paradox. Eurasian Heart Journal. 2018;25(1):121-39 (In Russ.)
5. Tatarsky BA, Batalov RE, Popov SV. Atrial fibrillation: pathophysiological approaches to the choice of antiarrhythmic therapy. Tomsk: STT, 2013 (In Russ.)
6. Unger RH. Lipotoxic diseases. Annu Rev Med. 2002;53:319-36. doi: 10.1146/annurev.med.53.082901.104057
7. Unger RH, Scherer PE. Gluttony, sloth and metabolic syndrome: a roadmap to lipotoxisity. Endocrinol Metab. 2010;21(6):345-52. doi: 10.1016/j.tem.2010.01.009
8. Brugada R, Hong K, Dumaine R, et al. Sudden death associated with short-QT syndrome linked to mutations in HERG. Circulation. 2014;109:30-5. doi: 10.1161/CIRCULATIONAHA.106.668392
9. Shulman VA, Nikulina SY, Aksyutina NV, et al. First Russia-based study of polymorphism rs2200733 chromosome 4q25 association with development of the lone atrial fibrillation. Russian Journal of Cardiology. 2016;10:28-31 (In Russ.) doi: 10.15829/1560-4071-2016-10-28-31
10. Jennsen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. JACC. 2014;63(25):2985-3023. Available at: https:www.acc./guidelines. doi: 10.1161/01.cir.0000437739.71477.ee
11. Coutinho T, Goel K, Corrêa de Sá D, et al. Combining Body Mass Index With Measures of Central Obesity in the Assessment of Mortality in Subjects With Coronary Disease: Role of “Normal Weight Central Obesity”. J Am Coll Cardiol. 2013;61(5):553-60. doi: 10.1016/j.jacc.2012.10.035
12. Sandhu RK, Ezekowitz J, Andersson U, et al. The “obesity paradox” in atrial fibrillation: observations from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Eur Heart J. 2016;37:2869-78. doi: 10.1093/eurheartj/ehw124
13. Littleton SW, Mokhlesi B. The pickwickian syndrome-obesity hypoventilation syndrome. Clin Chest Med. 2009; 30(3):467-78. doi: 10.1093/eurheartj/ehw124
14. Guidelines Committee. 2003 European Society of Hypertension-European Society of Cardiology guidelines for management of arterial hypertension. J Hypertens. 2013;21:1011-53. doi: 10.1097/HJH.0000000000000466
15. The Expert Panel. Third Report of the National cholesterol in Educational Program [NCEP] Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults [Adult Treatment Panel III] FinalReport. Circ. 2012;106:3143-421. doi: 10.1016/j.cccn.2004.08.012
16. Zafrir B, Adir Y, Shehadeh W, et al. The association between obesity, mortality and filling pressures in pulmonary hypertension patients; the «obesity paradox». Respir Med. 2013;107(1):139-46. doi: 0.1016/j.rmed.2012.10.019
17. Kirchhof P, Bax J, Blomstrom-Lundquist C, et al. Early and comprehensive management of atrial fibrillation: executive summary of the proceedings from the 2nd AFnEt-EHRA consensus conference ‘research perspectives in AF. Eur Heart J. 2009;30(24):2969-77. doi: 10.1093/eurheartj/ehp235
18. Rai R, Sharma KL, Misra S. CYP17 polymorphism [rs743572] is associated with increased risk of gallbladder cancer in tobacco users. Tumour Biol. 2014;35(7):6531-7. Available at: https:link.springer.com/article/
10.1007%2Fs13277-014-1876-2. doi: 10.1007/s13277-014-1876-2
19. Goodloe AH, Herron KJ, Olson TM. Uncovering an intermediate phenotype associated with rs2200733 at 4q25 in lone atrial fibrillation. Am J Cardiol. 2014;107(12):1802-5. doi: 10.1016%2Fj.amjcard.2013.08.045
2. Клинические рекомендации «Диагностика и лечение фибрилляции предсердий». М., 2017 [Clinical recommendations “Diagnosis and treatment of atrial fibrillation”. Moscow, 2017 (In Russ.)].
3. Thomas F, Bean K, Pannier B, et al. Cardiovascular mortality in overweight subjects. The key role of associated risk factors. Hypertension. 2005;46:654-63. doi: 10.1161/01.HYP.0000184282.51550.00
4. Хидирова Л.Д., Яхонтов Д.А., Куропий Т.С., Зенин С.А. Фибрилляция предсердий в сочетании с артериальной гипертонией и парадокс ожирения. Евразийский кардиологический журн. 2019;25(1):121-39 [Khidirova LD, Yakhontov DA, Kurope TS, Zenin SA. Atrial fibrillation in combination with arterial hypertension and obesity paradox. Eurasian Heart Journal. 2018;25(1):121-39 (In Russ.)].
5. Татарский Б.А., Баталов Р.Е., Попов С.В. Фибрилляция предсердий: патофизиологические подходы к выбору антиаритмической терапии. Томск: STT, 2013 [Tatarsky BA, Batalov RE, Popov SV. Atrial fibrillation: pathophysiological approaches to the choice of antiarrhythmic therapy. Tomsk: STT, 2013 (In Russ.)].
6. Unger RH. Lipotoxic diseases. Annu Rev Med. 2002;53:319-36. doi: 10.1146/annurev.med.53.082901.104057
7. Unger RH, Scherer PE. Gluttony, sloth and metabolic syndrome: a roadmap to lipotoxisity. Endocrinol Metab. 2010;21(6):345-52. doi: 10.1016/j.tem.2010.01.009
8. Brugada R, Hong K, Dumaine R, et al. Sudden death associated with short-QT syndrome linked to mutations in HERG. Circulation. 2014;109:30-5. doi: 10.1161/CIRCULATIONAHA.106.668392
9. Шульман В.А., Никулина С.Ю., Аксютина Н.В. и др. Первое российское исследование ассоциации полиморфизма rs2200733 хромосомы 4q25 с развитием изолированной фибрилляции предсердий. Рос. кардиол. журн. 2016;10:28-31 [Shulman VA, Nikulina SY, Aksyutina NV, et al. First Russia-based study of polymorphism rs2200733 chromosome 4q25 association with development of the lone atrial fibrillation. Russian Journal of Cardiology. 2016;10:28-31 (In Russ.)]. doi: 10.15829/1560-4071-2016-10-28-31
10. Jennsen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. JACC. 2014;63(25):2985-3023. Available at: https:www.acc./guidelines. doi: 10.1161/01.cir.0000437739.71477.ee
11. Coutinho T, Goel K, Corrêa de Sá D, et al. Combining Body Mass Index With Measures of Central Obesity in the Assessment of Mortality in Subjects With Coronary Disease: Role of “Normal Weight Central Obesity”. J Am Coll Cardiol. 2013;61(5):553-60. doi: 10.1016/j.jacc.2012.10.035
12. Sandhu RK, Ezekowitz J, Andersson U, et al. The “obesity paradox” in atrial fibrillation: observations from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Eur Heart J. 2016;37:2869-78. doi: 10.1093/eurheartj/ehw124
13. Littleton SW, Mokhlesi B. The pickwickian syndrome-obesity hypoventilation syndrome. Clin Chest Med. 2009; 30(3):467-78. doi: 10.1093/eurheartj/ehw124
14. Guidelines Committee. 2003 European Society of Hypertension-European Society of Cardiology guidelines for management of arterial hypertension. J Hypertens. 2013;21:1011-53. doi: 10.1097/HJH.0000000000000466
15. The Expert Panel. Third Report of the National cholesterol in Educational Program [NCEP] Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults [Adult Treatment Panel III] FinalReport. Circ. 2012;106:3143-421. doi: 10.1016/j.cccn.2004.08.012
16. Zafrir B, Adir Y, Shehadeh W, et al. The association between obesity, mortality and filling pressures in pulmonary hypertension patients; the «obesity paradox». Respir Med. 2013;107(1):139-46. doi: 0.1016/j.rmed.2012.10.019
17. Kirchhof P, Bax J, Blomstrom-Lundquist C, et al. Early and comprehensive management of atrial fibrillation: executive summary of the proceedings from the 2nd AFnEt-EHRA consensus conference ‘research perspectives in AF. Eur Heart J. 2009;30(24):2969-77. doi: 10.1093/eurheartj/ehp235
18. Rai R, Sharma KL, Misra S. CYP17 polymorphism [rs743572] is associated with increased risk of gallbladder cancer in tobacco users. Tumour Biol. 2014;35(7):6531-7. Available at: https:link.springer.com/article/
10.1007%2Fs13277-014-1876-2. doi: 10.1007/s13277-014-1876-2
19. Goodloe AH, Herron KJ, Olson TM. Uncovering an intermediate phenotype associated with rs2200733 at 4q25 in lone atrial fibrillation. Am J Cardiol. 2014;107(12):1802-5. doi: 10.1016%2Fj.amjcard.2013.08.045
________________________________________________
2. Клинические рекомендации «Диагностика и лечение фибрилляции предсердий». М., 2017 [Clinical recommendations “Diagnosis and treatment of atrial fibrillation”. Moscow, 2017 (In Russ.)].
3. Thomas F, Bean K, Pannier B, et al. Cardiovascular mortality in overweight subjects. The key role of associated risk factors. Hypertension. 2005;46:654-63. doi: 10.1161/01.HYP.0000184282.51550.00
4. Khidirova LD, Yakhontov DA, Kurope TS, Zenin SA. Atrial fibrillation in combination with arterial hypertension and obesity paradox. Eurasian Heart Journal. 2018;25(1):121-39 (In Russ.)
5. Tatarsky BA, Batalov RE, Popov SV. Atrial fibrillation: pathophysiological approaches to the choice of antiarrhythmic therapy. Tomsk: STT, 2013 (In Russ.)
6. Unger RH. Lipotoxic diseases. Annu Rev Med. 2002;53:319-36. doi: 10.1146/annurev.med.53.082901.104057
7. Unger RH, Scherer PE. Gluttony, sloth and metabolic syndrome: a roadmap to lipotoxisity. Endocrinol Metab. 2010;21(6):345-52. doi: 10.1016/j.tem.2010.01.009
8. Brugada R, Hong K, Dumaine R, et al. Sudden death associated with short-QT syndrome linked to mutations in HERG. Circulation. 2014;109:30-5. doi: 10.1161/CIRCULATIONAHA.106.668392
9. Shulman VA, Nikulina SY, Aksyutina NV, et al. First Russia-based study of polymorphism rs2200733 chromosome 4q25 association with development of the lone atrial fibrillation. Russian Journal of Cardiology. 2016;10:28-31 (In Russ.) doi: 10.15829/1560-4071-2016-10-28-31
10. Jennsen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. JACC. 2014;63(25):2985-3023. Available at: https:www.acc./guidelines. doi: 10.1161/01.cir.0000437739.71477.ee
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Авторы
Л.Д. Хидирова1, Д.А. Яхонтов1, В.Н. Максимов2
1 ФГБОУ ВО «Новосибирский государственный медицинский университет» Минздрава России, Новосибирск, Россия;
2 Научно-исследовательский институт терапии и профилактической медицины – филиал ФГБНУ «Федеральный исследовательский центр "Институт цитологии и генетики"» Сибирского отделения Российской академии наук, Новосибирск, Россия
1 Novosibirsk State Medical University, Novosibirsk, Russia;
2 Institute of Internal and Preventive Medicine – branch of the Federal Research Center Institute of Cytology and Genetics, Novosibirsk, Russia
1 ФГБОУ ВО «Новосибирский государственный медицинский университет» Минздрава России, Новосибирск, Россия;
2 Научно-исследовательский институт терапии и профилактической медицины – филиал ФГБНУ «Федеральный исследовательский центр "Институт цитологии и генетики"» Сибирского отделения Российской академии наук, Новосибирск, Россия
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1 Novosibirsk State Medical University, Novosibirsk, Russia;
2 Institute of Internal and Preventive Medicine – branch of the Federal Research Center Institute of Cytology and Genetics, Novosibirsk, Russia
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