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Этногенетические аспекты ожирения и нарушений углеводного обмена как факторов риска артериальной гипертензии
Этногенетические аспекты ожирения и нарушений углеводного обмена как факторов риска артериальной гипертензии
Мулерова Т.А., Цыганкова Д.П., Воропаева Е.Н. и др. Этногенетические аспекты ожирения и нарушений углеводного обмена как факторов риска артериальной гипертензии. Системные гипертензии. 2016; 13 (3): 48–57.
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Аннотация
Цель – изучить ассоциации генов-кандидатов артериальной гипертензии (АГ): ACE, ADRA2B, ADRB1, MTHFR и eNOS – с ожирением и нарушениями углеводного обмена с учетом этнической принадлежности.
Материал и методы. Проведено клинико-эпидемиологическое исследование компактно проживающего населения в труднодоступных районах Горной Шории (п. Ортон, п. Усть-Кабырза, п. Шерегеш Кемеровской области). Сплошным методом обследованы 1178 жителей указанных поселков, выборка состояла из взрослого населения (18 лет и старше).
Результаты. В группе респондентов коренной национальности средние величины индекса Кетле, окружности талии и глюкозы крови натощак в зависимости от полиморфизма генов-кандидатов АГ – ACE, ADRA2B, ADRB1, MTHFR и eNOS – оказались ниже, чем в группе обследованных некоренного этноса. В популяции шорцев была выявлена статистически значимая взаимосвязь индекса Кетле с генотипами гена AСЕ, в популяции некоренных представителей – с генотипами гена ADRA2B. В группе коренного этноса выявлена взаимосвязь окружности талии с полиморфизмом гена АСЕ. Независимо от национальной принадлежности выявлена ассоциативная связь данного показателя с полиморфизмом гена ADRA2B. Уровень глюкозы плазмы в популяции некоренного этноса был взаимосвязан с генотипами гена ADRA2B.
Заключение. Метаболические нарушения были выявлены реже в коренной этнической группе по сравнению с представителями некоренной национальности. В группе шорцев генотипы DD генов АСЕ и ADRA2B ассоциировались с ожирением, генотип 4а/4а гена eNOS – с абдоминальным ожирением. В группе некоренного этноса генотип СС гена MTHFR ассоциировался с абдоминальным ожирением, генотипы II гена АСЕ и DD гена ADRA2B – с нарушениями углеводного обмена.
Ключевые слова: этнос, факторы риска, гены-кандидаты, ассоциации, I/D-полиморфизм, ген эндотелиальной синтетазы.
Materials and methods. Clinical and epidemiological study of compactly living population in the remote areas of the Mountain Shoria (Orton, Ust-Kabyrza, Sheregesh settlements, Kemerovo region). 1178 residents of these settlements were surveyed with the help of continuous sampling method; the sample consisted of adults (18 years and older).
Results. In the group of respondents of the indigenous nationality averages Quetelet index, waist circumference and fasting blood glucose, depending on the polymorphism of candidate genes of arterial hypertension ACE, ADRA2B, ADRB1, MTHFR and eNOS were lower than in non-indigenous ethnic group surveyed. In a population of Shor was found a statistically significant relationship with the body mass index of ACE gene genotypes in a population of non-indigenous representatives – with genotypes of ADRA2B gene. In the group of indigenous ethnic group revealed the relationship from ACE gene polymorphism. Regardless of nationality, found associative connection of the indicator polymorphism of ADRA2B gene. The level of plasma glucose levels in a population of non-indigenous ethnic group was correlated with genotypes of ADRA2B gene.
Conclusion. Metabolic abnormalities were detected less frequently in indigenous ethnic group compared with the non-indigenous. In Shor group ACE DD genotype and ADRA2B genes associated with obesity, the genotype 4a/4a eNOS gene – with abdominal obesity. In the group of non-indigenous ethnic group CC genotype of the MTHFR gene was associated with abdominal obesity, II genotype of ACE gene and DD ADRA2B gene – with impaired carbohydrate metabolism.
Key words: ethnicity, risk factors, candidate genes, association, I/D polymorphism, endothelial synthase gene.
Материал и методы. Проведено клинико-эпидемиологическое исследование компактно проживающего населения в труднодоступных районах Горной Шории (п. Ортон, п. Усть-Кабырза, п. Шерегеш Кемеровской области). Сплошным методом обследованы 1178 жителей указанных поселков, выборка состояла из взрослого населения (18 лет и старше).
Результаты. В группе респондентов коренной национальности средние величины индекса Кетле, окружности талии и глюкозы крови натощак в зависимости от полиморфизма генов-кандидатов АГ – ACE, ADRA2B, ADRB1, MTHFR и eNOS – оказались ниже, чем в группе обследованных некоренного этноса. В популяции шорцев была выявлена статистически значимая взаимосвязь индекса Кетле с генотипами гена AСЕ, в популяции некоренных представителей – с генотипами гена ADRA2B. В группе коренного этноса выявлена взаимосвязь окружности талии с полиморфизмом гена АСЕ. Независимо от национальной принадлежности выявлена ассоциативная связь данного показателя с полиморфизмом гена ADRA2B. Уровень глюкозы плазмы в популяции некоренного этноса был взаимосвязан с генотипами гена ADRA2B.
Заключение. Метаболические нарушения были выявлены реже в коренной этнической группе по сравнению с представителями некоренной национальности. В группе шорцев генотипы DD генов АСЕ и ADRA2B ассоциировались с ожирением, генотип 4а/4а гена eNOS – с абдоминальным ожирением. В группе некоренного этноса генотип СС гена MTHFR ассоциировался с абдоминальным ожирением, генотипы II гена АСЕ и DD гена ADRA2B – с нарушениями углеводного обмена.
Ключевые слова: этнос, факторы риска, гены-кандидаты, ассоциации, I/D-полиморфизм, ген эндотелиальной синтетазы.
________________________________________________
Materials and methods. Clinical and epidemiological study of compactly living population in the remote areas of the Mountain Shoria (Orton, Ust-Kabyrza, Sheregesh settlements, Kemerovo region). 1178 residents of these settlements were surveyed with the help of continuous sampling method; the sample consisted of adults (18 years and older).
Results. In the group of respondents of the indigenous nationality averages Quetelet index, waist circumference and fasting blood glucose, depending on the polymorphism of candidate genes of arterial hypertension ACE, ADRA2B, ADRB1, MTHFR and eNOS were lower than in non-indigenous ethnic group surveyed. In a population of Shor was found a statistically significant relationship with the body mass index of ACE gene genotypes in a population of non-indigenous representatives – with genotypes of ADRA2B gene. In the group of indigenous ethnic group revealed the relationship from ACE gene polymorphism. Regardless of nationality, found associative connection of the indicator polymorphism of ADRA2B gene. The level of plasma glucose levels in a population of non-indigenous ethnic group was correlated with genotypes of ADRA2B gene.
Conclusion. Metabolic abnormalities were detected less frequently in indigenous ethnic group compared with the non-indigenous. In Shor group ACE DD genotype and ADRA2B genes associated with obesity, the genotype 4a/4a eNOS gene – with abdominal obesity. In the group of non-indigenous ethnic group CC genotype of the MTHFR gene was associated with abdominal obesity, II genotype of ACE gene and DD ADRA2B gene – with impaired carbohydrate metabolism.
Key words: ethnicity, risk factors, candidate genes, association, I/D polymorphism, endothelial synthase gene.
Полный текст
Список литературы
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2. Burkova G., Ivleva A.Ya. Overweight and obesity – the problem is medical, rather than cosmetic. Obesity and Metabolism. 2010; 3: 15–9. [in Russian]
3. Babin A.G., Chechetkina E.A., Koltunov I.E. Psychosomatic aspects of obesity as a risk factor of metabolic syndrome. Cardiovascular Therapy and Prevention. 2010; 7 (9): 71–8. [in Russian]
4. Chumakova G.A., Veselovskaya N.G., Kozarenko A.A. The morphology, structure and function of the heart in obesity. Journal of Cardiology. 2012; 4: 93–9. [in Russian]
5. Astashkin E.I., Gleser M.G. Obesity and hypertension. Women's Health Issues. 2008; 3 (4): 23–33. [in Russian]
6. Vasilkova T.N., Mataev S.I., Baklaeva T.B. Effect of different types of fat deposition in the cardiovascular system. Heart: a magazine for practicing physicians. 2014; 1(13): 45–9. [in Russian]
7. Cornier MA, Després JP, Davis N et al/ Assessing adiposity: a scientific statement from the American Heart Association. Circulation 2011; 124 (18): 1996–2019.
8. Guoheng X. Role of perilipin phosphorylation on the control of lipolysis in adipocytes. Chin J Pathophysiol 2006; 22 (13): 69.
9. Kado DM, Huang MH, Barrett-Connor E, Greendale GA. Hyperkyphotic posture and poor physical functional ability in older community-dwelling men and women: the rancho bernardo study. J Gerontol A Biol Sci Med Sci 2005; 60 (5): 633–7.
10. Tuomilehto J, Borch-Johnsen K, Pyorala K. European Diabetes Epidemiology Group. Prediction of the risk of cardiovascular mortality using a score that includes glucose as a risk factor. The DECODE Study. Diabetologia 2004; 47 (12): 2118–28.
11. Gorbunova V.N. Genetics and epigenetics commensal disease. Ecological genetics. 2010; 8 (4): 39–43. [in Russian]
12. Binder A. Identification of genes for a complex trait: examples from hypertension. Curr Pharm Biotechnol 2006; 7 (1): 1–13.
13. Cоwlеy АW. Thе gеnеtic dissеctiоn оf еssеntiаl hyреrtеnsiоn. Nаturе Rеv Gеnеtics 2006; 7 (11): 829–40.
14. Еichlеr ЕЕ. Missing hеritаbility аnd strаtеgiеs fоr finding thе undеrlying cаusеs оf cоmрlех disеаsе. Nаt Rеv Gеnеt 2010; 11 (6): 446–50.
15. Snapir A, Scheinin M, Groop LC, Orho-Melander M. The insertion/deletion variation in the α2B-adrenoceptor does not seem to modify the risk for acute myocardial infarction, but may modify the risk for hypertension in sib-pairs from families with type 2 diabetes. Cardiovasc Diabetol 2003; 2: 15.
16. Lima JJ, Feng H, Duckworth L et al. Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations. Metabolism 2007; 56 (6): 757–65.
17. Salimi S, Firoozrai M, Nourmohammadi I et al. Endothelial nitric oxide synthase gene intron4 VNTR polymorphism in patients with coronary artery disease in Iran. Indian J Med Res 2006; 124 (6): 683–8.
18. Scott HA, Gibson PG, Garg ML, Wood LG. Airway inflammation is augmented by obesity and fatty acids in asthma. Eur Respir J 2011; 38(3): 594–602.
19. de Koning L, Merchant AT, Pogue J, Anand SS. Waist circumference and waist-to-hip ratio as predictors of cardiovascular events: meta-regression analysis of prospective studies. Eur Heart J 2007; 28 (7): 850–6.
20. Konstantinov V.V., Deev A.D., Kapustin A.A. Prevalence of overweight and its association with mortality from cardiovascular and other chronic non-communicable diseases among the male population in cities of different regions. Cardiology. 2002; 10: 45–9. [in Russian]
21. Uemura K, Nakura J, Kohara K, Miki T. Association of ACE I/D polymorphism with cardiovascular risk factors. Hum Genet 2000; 107 (3): 239–42.
22. Mittal G, Gupta V, Haque SF, Khan AS. Effect of angiotensin converting enzyme gene I/D polymorphism in patients with metabolic syndrome in North Indian population. Chin Med J (Engl) 2011; 124 (1): 45–8.
23. Shunmugam V, Say YH. Evaluation of Association of ADRA2A rs553668 and ACE I/D Gene Polymorphisms with Obesity Traits in the Setapak Population, Malaysia. Iran Red Crescent Med J 2016; 18 (2): e22452.
24. Mao S, Huang S. A meta-analysis of the association between angiotensin-converting enzyme insertion/deletion gene polymorphism and the risk of overweight/obesity. J Renin Angiotensin Aldosterone Syst 2015; 16 (3): 687–94.
25. Pacholczyk M, Ferenc T, Kowalski J et al. Association of angiotensin-converting enzyme and angiotensin II type I receptor gene polymorphisms with extreme obesity in Polish individuals. DNA Cell Biol 2013; 32 (8): 435–42.
26. Das M, Pal S, Ghosh A. Synergistic effects of ACE (I/D) and Apo E (Hha I) gene polymorphisms on obesity, fat mass, and blood glucose level among the adult Asian Indians: A population-based study from Calcutta, India. Indian J Endocrinol Metab 2013; 17 (1): 101–4.
27. Kim K. Association of angiotensin-converting enzyme insertion/deletion polymorphism with obesity, cardiovascular risk factors and exercise-mediated changes in Korean women. Eur J Appl Physiol 2009; 105 (6): 879–87.
28. Suchánek P, Hubácek JA, Králová Lesná I et al. Actigenetic of ACE gene polymo-rphism in Czech obese sedentary females. Physiol Res 2009; 58 (Suppl. 1): S47–52.
29. Suzuki N, Matsunaga T, Nagasumi K et al. Alpha(2B)-adrenergic receptor deletion polymorphism associates with autonomic nervous system activity in young healthy Japanese. J Clin Endocrinol Metab 2003; 88 (3): 1184–7.
30. Fava C, Montagnana M, Guerriero M et al. Chromosome 2q12, the ADRA2B I/D polymorphism and metabolic syndrome. J Hypertens 2009; 27 (9): 1794–803.
31. Etzel JP, Rana BK, Wen G et al. Genetic variation at the human alpha2B-adrenergic receptor locus: role in blood pressure variation and yohimbine response. Hypertension 2005; 45 (6): 1207–13.
32. Laukkanen JA, Mäkikallio TH, Kauhanen J, Kurl S. Insertion/deletion polymor-phism in alpha2-adrenergic receptor gene is a genetic risk factor for sudden cardiac death. Am Heart J 2009; 158 (4): 615–21.
33. Zhang H, Li X, Huang J et al. Cardiovascular and metabolic phenotypes in relation to the ADRA2B insertion/deletion polymorphism in a Chinese population. J Hypertens 2005; 23 (12): 2201–7.
34. Papanas N, Papatheodorou K, Papazoglou D et al. An insertion/deletion polymorphism in the alpha2B adrenoceptor gene is associated with peripheral neuropathy in patients with type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes 2007; 115 (5): 327–30.
35. Sykiotis GP, Polyzogopoulou E, Georgopoulos NA et al. The alpha2B adrenergic receptor deletion/insertion polymorphism in morbid obesity. Clin Auton Res 2003; 13 (3): 203–7.
36. Vasudevan R, Ismail P, Stanslas J et al. Association of insertion/deletion polymorphism of alpha-adrenoceptor gene in essential hypertension with or without type 2 diabetes mellitus in Malaysian subjects. Int J Biol Sci 2008; 4 (6): 362–7.
37. Dionne IJ, Garant MJ, Nolan AA et al. Association between obesity and a polymorphism in the beta(1)-adrenoceptor gene (Gly389Arg ADRB1) in Caucasian women. Int J Obes Relat Metab Dis 2002; 26 (5): 633–9.
38. Linné Y, Dahlman I, Hoffstedt J. Beta1-Adrenoceptor gene polymorphism predicts long-term changes in body weight. Int J Obes (Lond) 2005; 29 (5): 458–62.
39. Voevoda M.I., Maksimov V.N., Kulikov I.V. Sudden cardi ac death and polymorphism of candidate genes for cardiovascular disease MEA. Novosibirsk, 2006; p. 23–7. [in Russian]
40. Mottagui-Tabar S, Hoffstedt J, Brookes AJ et al. Association of ADRB1 and UCP3 gene polymorphisms with insulin sensitivity but not obesity. Horm Res 2008; 69 (1): 31–6.
41. Gjesing AP, Andersen G, Albrechtsen A et al. Studies of associations between the Arg389Gly polymorphism of the beta1-adrenergic receptor gene (ADRB1) and hypertension and obesity in 7677 Danish white subjects. Diabet Med 2007; 24(4): 392–7.
42. Terra SG, McGorray SP, Wu R et al. Association between beta-adrenergic receptor polymorphisms and their G-protein-coupled receptors with body mass index and obesity in women: a report from the NHLBI-sponsored WISE study. Int J Obes (Lond) 2005; 29 (7): 746–54.
43. Souza-Costa DC, Belo VA, Silva PS et al. eNOS haplotype associated with hypertension in obese children and adolescents. Int J Obes (Lond) 2011; 35 (3): 387–92.
44. Hoffmann IS, Tavares-Mordwinkin R, Castejon AM et al. Endothelial nitric oxide synthase polymorphism, nitric oxide production, salt sensitivity and cardiovascular risk factors in Hispanics. J Hum Hypertens 2005; 19 (3): 233–40.
45. Miranda JA, Belo VA, Souza-Costa DC et al. eNOS polymorphism associated with metabolic syndrome in children and adolescents. Mol Cell Biochem 2013; 372 (1–2): 155–60.
46. Kucukhuseyin O, Kurnaz O, Akadam-Teker AB et al. The association of MTHFR C677T gene variants and lipid profiles or body mass index in patients with diabetic and nondiabetic coronary heart disease. J Clin Lab Anal 2013; 27 (6): 427–34.
47. Yang B, Fan S, Zhi X et al. Associations of MTHFR C677T and MTRR A66G gene polymorphisms with metabolic syndrome: a case-control study in Northern China. Int J Mol Sci 2014; 15 (12): 21687–702.
48. Chen AR, Zhang HG, Wang ZP et al. C-reactive protein, vitamin B12 and C677T polymorphism of N-5,10-methylenetetrahydrofolate reductase gene are related to insulin resistance and risk factors for metabolic syndrome in Chinese population. Clin Invest Med 2010; 33 (5): E290–297.
49. Fan S, Yang B, Zhi X et al. Interactions of Methylenetetrahydrofolate Reductase C677T Polymorphism with Environmental Factors on Hypertension Susceptibility. Int J Environ Res Public Health 2016; 13 (6). pii: E601.
50. Russo GT, Di Benedetto A, Alessi E et al. Mild hyperhomocysteinemia and the common C677T polymorphism of methylene tetrahydrofolate reductase gene are not associated with the metabolic syndrome in Type 2 diabetes. J Endocrinol Invest 2006; 29 (3): 201–7.
51. Uehara SK, Rosa G. Association of homocysteinemia with high concentrations of serum insulin and uric acid in Brazilian subjects with metabolic syndrome genotyped for C677T polymorphism in the methylenetetrahydrofolate reductase gene. Nutr Res 2008; 28 (11): 760–6.
2. Бурков Г., Ивлева А.Я. Избыточный вес и ожирение – проблема медицинская, а не косметическая. Ожирение и метаболизм. 2010; 3: 15–9. / Burkova G., Ivleva A.Ya. Overweight and obesity – the problem is medical, rather than cosmetic. Obesity and Metabolism. 2010; 3: 15–9. [in Russian]
3. Бабин А.Г., Чечеткина Е.А., Колтунов И.Е. Психосоматический аспект ожирения как фактор риска метаболического синдрома. Кардиоваскулярная терапия и профилактика. 2010; 7 (9): 71–8. / Babin A.G., Chechetkina E.A., Koltunov I.E. Psychosomatic aspects of obesity as a risk factor of metabolic syndrome. Cardiovascular Therapy and Prevention. 2010; 7 (9): 71–8. [in Russian]
4. Чумакова Г.А., Веселовская Н.Г., Козаренко А.А. Особенности морфологии, структуры и функции сердца при ожирении. Рос. кардиологический журн. 2012; 4: 93–9. / Chumakova G.A., Veselovskaya N.G., Kozarenko A.A. The morphology, structure and function of the heart in obesity. Journal of Cardiology. 2012; 4: 93–9. [in Russian]
5. Асташкин Е.И., Глезер М.Г. Ожирение и артериальная гипертония. Проблемы женского здоровья. 2008; 3 (4): 23–33. / Astashkin E.I., Gleser M.G. Obesity and hypertension. Women's Health Issues. 2008; 3 (4): 23–33. [in Russian]
6. Василькова Т.Н., Матаев С.И., Баклаева Т.Б. Влияние различных типов жироотложения на состояние сердечно-сосудистой системы. Сердце: журнал для практикующих врачей. 2014; 1 (13): 45–9. / Vasilkova T.N., Mataev S.I., Baklaeva T.B. Effect of different types of fat deposition in the cardiovascular system. Heart: a magazine for practicing physicians. 2014; 1(13): 45–9. [in Russian]
7. Cornier MA, Després JP, Davis N et al/ Assessing adiposity: a scientific statement from the American Heart Association. Circulation 2011; 124 (18): 1996–2019.
8. Guoheng X. Role of perilipin phosphorylation on the control of lipolysis in adipocytes. Chin J Pathophysiol 2006; 22 (13): 69.
9. Kado DM, Huang MH, Barrett-Connor E, Greendale GA. Hyperkyphotic posture and poor physical functional ability in older community-dwelling men and women: the rancho bernardo study. J Gerontol A Biol Sci Med Sci 2005; 60 (5): 633–7.
10. Tuomilehto J, Borch-Johnsen K, Pyorala K. European Diabetes Epidemiology Group. Prediction of the risk of cardiovascular mortality using a score that includes glucose as a risk factor. The DECODE Study. Diabetologia 2004; 47 (12): 2118–28.
11. Горбунова В.Н. Генетика и эпигенетика синтропных заболеваний. Экологическая генетика. 2010; 8 (4): 39–43. / Gorbunova V.N. Genetics and epigenetics commensal disease. Ecological genetics. 2010; 8 (4): 39–43. [in Russian]
12. Binder A. Identification of genes for a complex trait: examples from hypertension. Curr Pharm Biotechnol 2006; 7 (1): 1–13.
13. Cоwlеy АW. Thе gеnеtic dissеctiоn оf еssеntiаl hyреrtеnsiоn. Nаturе Rеv Gеnеtics 2006; 7 (11): 829–40.
14. Еichlеr ЕЕ. Missing hеritаbility аnd strаtеgiеs fоr finding thе undеrlying cаusеs оf cоmрlех disеаsе. Nаt Rеv Gеnеt 2010; 11 (6): 446–50.
15. Snapir A, Scheinin M, Groop LC, Orho-Melander M. The insertion/deletion variation in the α2B-adrenoceptor does not seem to modify the risk for acute myocardial infarction, but may modify the risk for hypertension in sib-pairs from families with type 2 diabetes. Cardiovasc Diabetol 2003; 2: 15.
16. Lima JJ, Feng H, Duckworth L et al. Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations. Metabolism 2007; 56 (6): 757–65.
17. Salimi S, Firoozrai M, Nourmohammadi I et al. Endothelial nitric oxide synthase gene intron4 VNTR polymorphism in patients with coronary artery disease in Iran. Indian J Med Res 2006; 124 (6): 683–8.
18. Scott HA, Gibson PG, Garg ML, Wood LG. Airway inflammation is augmented by obesity and fatty acids in asthma. Eur Respir J 2011; 38(3): 594–602.
19. de Koning L, Merchant AT, Pogue J, Anand SS. Waist circumference and waist-to-hip ratio as predictors of cardiovascular events: meta-regression analysis of prospective studies. Eur Heart J 2007; 28 (7): 850–6.
20. Константинов В.В., Деев А.Д., Капустина А.А. Распространенность избыточной массы тела и ее связь со смертностью от сердечно-сосудистых и других хронических неинфекционных заболеваний среди мужского населения в городах разных регионов. Кардиология. 2002; 10: 45–9. / Konstantinov V.V., Deev A.D., Kapustin A.A. Prevalence of overweight and its association with mortality from cardiovascular and other chronic non-communicable diseases among the male population in cities of different regions. Cardiology. 2002; 10: 45–9. [in Russian]
21. Uemura K, Nakura J, Kohara K, Miki T. Association of ACE I/D polymorphism with cardiovascular risk factors. Hum Genet 2000; 107 (3): 239–42.
22. Mittal G, Gupta V, Haque SF, Khan AS. Effect of angiotensin converting enzyme gene I/D polymorphism in patients with metabolic syndrome in North Indian population. Chin Med J (Engl) 2011; 124 (1): 45–8.
23. Shunmugam V, Say YH. Evaluation of Association of ADRA2A rs553668 and ACE I/D Gene Polymorphisms with Obesity Traits in the Setapak Population, Malaysia. Iran Red Crescent Med J 2016; 18 (2): e22452.
24. Mao S, Huang S. A meta-analysis of the association between angiotensin-converting enzyme insertion/deletion gene polymorphism and the risk of overweight/obesity. J Renin Angiotensin Aldosterone Syst 2015; 16 (3): 687–94.
25. Pacholczyk M, Ferenc T, Kowalski J et al. Association of angiotensin-converting enzyme and angiotensin II type I receptor gene polymorphisms with extreme obesity in Polish individuals. DNA Cell Biol 2013; 32 (8): 435–42.
26. Das M, Pal S, Ghosh A. Synergistic effects of ACE (I/D) and Apo E (Hha I) gene polymorphisms on obesity, fat mass, and blood glucose level among the adult Asian Indians: A population-based study from Calcutta, India. Indian J Endocrinol Metab 2013; 17 (1): 101–4.
27. Kim K. Association of angiotensin-converting enzyme insertion/deletion polymorphism with obesity, cardiovascular risk factors and exercise-mediated changes in Korean women. Eur J Appl Physiol 2009; 105 (6): 879–87.
28. Suchánek P, Hubácek JA, Králová Lesná I et al. Actigenetic of ACE gene polymo-rphism in Czech obese sedentary females. Physiol Res 2009; 58 (Suppl. 1): S47–52.
29. Suzuki N, Matsunaga T, Nagasumi K et al. Alpha(2B)-adrenergic receptor deletion polymorphism associates with autonomic nervous system activity in young healthy Japanese. J Clin Endocrinol Metab 2003; 88 (3): 1184–7.
30. Fava C, Montagnana M, Guerriero M et al. Chromosome 2q12, the ADRA2B I/D polymorphism and metabolic syndrome. J Hypertens 2009; 27 (9): 1794–803.
31. Etzel JP, Rana BK, Wen G et al. Genetic variation at the human alpha2B-adrenergic receptor locus: role in blood pressure variation and yohimbine response. Hypertension 2005; 45 (6): 1207–13.
32. Laukkanen JA, Mäkikallio TH, Kauhanen J, Kurl S. Insertion/deletion polymor-phism in alpha2-adrenergic receptor gene is a genetic risk factor for sudden cardiac death. Am Heart J 2009; 158 (4): 615–21.
33. Zhang H, Li X, Huang J et al. Cardiovascular and metabolic phenotypes in relation to the ADRA2B insertion/deletion polymorphism in a Chinese population. J Hypertens 2005; 23 (12): 2201–7.
34. Papanas N, Papatheodorou K, Papazoglou D et al. An insertion/deletion polymorphism in the alpha2B adrenoceptor gene is associated with peripheral neuropathy in patients with type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes 2007; 115 (5): 327–30.
35. Sykiotis GP, Polyzogopoulou E, Georgopoulos NA et al. The alpha2B adrenergic receptor deletion/insertion polymorphism in morbid obesity. Clin Auton Res 2003; 13 (3): 203–7.
36. Vasudevan R, Ismail P, Stanslas J et al. Association of insertion/deletion polymorphism of alpha-adrenoceptor gene in essential hypertension with or without type 2 diabetes mellitus in Malaysian subjects. Int J Biol Sci 2008; 4 (6): 362–7.
37. Dionne IJ, Garant MJ, Nolan AA et al. Association between obesity and a polymorphism in the beta(1)-adrenoceptor gene (Gly389Arg ADRB1) in Caucasian women. Int J Obes Relat Metab Dis 2002; 26 (5): 633–9.
38. Linné Y, Dahlman I, Hoffstedt J. Beta1-Adrenoceptor gene polymorphism predicts long-term changes in body weight. Int J Obes (Lond) 2005; 29 (5): 458–62.
39. Воевода М.И., Максимов В.Н., Куликов И.В. Внезапная сердечная смерть и полиморфизм генов-кандидатов сердечно-сосудистых заболеваний. СМЭ Новосибирск, 2006; с. 23–7. / Voevoda M.I., Maksimov V.N., Kulikov I.V. Sudden cardi ac death and polymorphism of candidate genes for cardiovascular disease MEA. Novosibirsk, 2006; p. 23–7. [in Russian]
40. Mottagui-Tabar S, Hoffstedt J, Brookes AJ et al. Association of ADRB1 and UCP3 gene polymorphisms with insulin sensitivity but not obesity. Horm Res 2008; 69 (1): 31–6.
41. Gjesing AP, Andersen G, Albrechtsen A et al. Studies of associations between the Arg389Gly polymorphism of the beta1-adrenergic receptor gene (ADRB1) and hypertension and obesity in 7677 Danish white subjects. Diabet Med 2007; 24(4): 392–7.
42. Terra SG, McGorray SP, Wu R et al. Association between beta-adrenergic receptor polymorphisms and their G-protein-coupled receptors with body mass index and obesity in women: a report from the NHLBI-sponsored WISE study. Int J Obes (Lond) 2005; 29 (7): 746–54.
43. Souza-Costa DC, Belo VA, Silva PS et al. eNOS haplotype associated with hypertension in obese children and adolescents. Int J Obes (Lond) 2011; 35 (3): 387–92.
44. Hoffmann IS, Tavares-Mordwinkin R, Castejon AM et al. Endothelial nitric oxide synthase polymorphism, nitric oxide production, salt sensitivity and cardiovascular risk factors in Hispanics. J Hum Hypertens 2005; 19 (3): 233–40.
45. Miranda JA, Belo VA, Souza-Costa DC et al. eNOS polymorphism associated with metabolic syndrome in children and adolescents. Mol Cell Biochem 2013; 372 (1–2): 155–60.
46. Kucukhuseyin O, Kurnaz O, Akadam-Teker AB et al. The association of MTHFR C677T gene variants and lipid profiles or body mass index in patients with diabetic and nondiabetic coronary heart disease. J Clin Lab Anal 2013; 27 (6): 427–34.
47. Yang B, Fan S, Zhi X et al. Associations of MTHFR C677T and MTRR A66G gene polymorphisms with metabolic syndrome: a case-control study in Northern China. Int J Mol Sci 2014; 15 (12): 21687–702.
48. Chen AR, Zhang HG, Wang ZP et al. C-reactive protein, vitamin B12 and C677T polymorphism of N-5,10-methylenetetrahydrofolate reductase gene are related to insulin resistance and risk factors for metabolic syndrome in Chinese population. Clin Invest Med 2010; 33 (5): E290–297.
49. Fan S, Yang B, Zhi X et al. Interactions of Methylenetetrahydrofolate Reductase C677T Polymorphism with Environmental Factors on Hypertension Susceptibility. Int J Environ Res Public Health 2016; 13 (6). pii: E601.
50. Russo GT, Di Benedetto A, Alessi E et al. Mild hyperhomocysteinemia and the common C677T polymorphism of methylene tetrahydrofolate reductase gene are not associated with the metabolic syndrome in Type 2 diabetes. J Endocrinol Invest 2006; 29 (3): 201–7.
51. Uehara SK, Rosa G. Association of homocysteinemia with high concentrations of serum insulin and uric acid in Brazilian subjects with metabolic syndrome genotyped for C677T polymorphism in the methylenetetrahydrofolate reductase gene. Nutr Res 2008; 28 (11): 760–6.
________________________________________________
2. Burkova G., Ivleva A.Ya. Overweight and obesity – the problem is medical, rather than cosmetic. Obesity and Metabolism. 2010; 3: 15–9. [in Russian]
3. Babin A.G., Chechetkina E.A., Koltunov I.E. Psychosomatic aspects of obesity as a risk factor of metabolic syndrome. Cardiovascular Therapy and Prevention. 2010; 7 (9): 71–8. [in Russian]
4. Chumakova G.A., Veselovskaya N.G., Kozarenko A.A. The morphology, structure and function of the heart in obesity. Journal of Cardiology. 2012; 4: 93–9. [in Russian]
5. Astashkin E.I., Gleser M.G. Obesity and hypertension. Women's Health Issues. 2008; 3 (4): 23–33. [in Russian]
6. Vasilkova T.N., Mataev S.I., Baklaeva T.B. Effect of different types of fat deposition in the cardiovascular system. Heart: a magazine for practicing physicians. 2014; 1(13): 45–9. [in Russian]
7. Cornier MA, Després JP, Davis N et al/ Assessing adiposity: a scientific statement from the American Heart Association. Circulation 2011; 124 (18): 1996–2019.
8. Guoheng X. Role of perilipin phosphorylation on the control of lipolysis in adipocytes. Chin J Pathophysiol 2006; 22 (13): 69.
9. Kado DM, Huang MH, Barrett-Connor E, Greendale GA. Hyperkyphotic posture and poor physical functional ability in older community-dwelling men and women: the rancho bernardo study. J Gerontol A Biol Sci Med Sci 2005; 60 (5): 633–7.
10. Tuomilehto J, Borch-Johnsen K, Pyorala K. European Diabetes Epidemiology Group. Prediction of the risk of cardiovascular mortality using a score that includes glucose as a risk factor. The DECODE Study. Diabetologia 2004; 47 (12): 2118–28.
11. Gorbunova V.N. Genetics and epigenetics commensal disease. Ecological genetics. 2010; 8 (4): 39–43. [in Russian]
12. Binder A. Identification of genes for a complex trait: examples from hypertension. Curr Pharm Biotechnol 2006; 7 (1): 1–13.
13. Cоwlеy АW. Thе gеnеtic dissеctiоn оf еssеntiаl hyреrtеnsiоn. Nаturе Rеv Gеnеtics 2006; 7 (11): 829–40.
14. Еichlеr ЕЕ. Missing hеritаbility аnd strаtеgiеs fоr finding thе undеrlying cаusеs оf cоmрlех disеаsе. Nаt Rеv Gеnеt 2010; 11 (6): 446–50.
15. Snapir A, Scheinin M, Groop LC, Orho-Melander M. The insertion/deletion variation in the α2B-adrenoceptor does not seem to modify the risk for acute myocardial infarction, but may modify the risk for hypertension in sib-pairs from families with type 2 diabetes. Cardiovasc Diabetol 2003; 2: 15.
16. Lima JJ, Feng H, Duckworth L et al. Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations. Metabolism 2007; 56 (6): 757–65.
17. Salimi S, Firoozrai M, Nourmohammadi I et al. Endothelial nitric oxide synthase gene intron4 VNTR polymorphism in patients with coronary artery disease in Iran. Indian J Med Res 2006; 124 (6): 683–8.
18. Scott HA, Gibson PG, Garg ML, Wood LG. Airway inflammation is augmented by obesity and fatty acids in asthma. Eur Respir J 2011; 38(3): 594–602.
19. de Koning L, Merchant AT, Pogue J, Anand SS. Waist circumference and waist-to-hip ratio as predictors of cardiovascular events: meta-regression analysis of prospective studies. Eur Heart J 2007; 28 (7): 850–6.
20. Konstantinov V.V., Deev A.D., Kapustin A.A. Prevalence of overweight and its association with mortality from cardiovascular and other chronic non-communicable diseases among the male population in cities of different regions. Cardiology. 2002; 10: 45–9. [in Russian]
21. Uemura K, Nakura J, Kohara K, Miki T. Association of ACE I/D polymorphism with cardiovascular risk factors. Hum Genet 2000; 107 (3): 239–42.
22. Mittal G, Gupta V, Haque SF, Khan AS. Effect of angiotensin converting enzyme gene I/D polymorphism in patients with metabolic syndrome in North Indian population. Chin Med J (Engl) 2011; 124 (1): 45–8.
23. Shunmugam V, Say YH. Evaluation of Association of ADRA2A rs553668 and ACE I/D Gene Polymorphisms with Obesity Traits in the Setapak Population, Malaysia. Iran Red Crescent Med J 2016; 18 (2): e22452.
24. Mao S, Huang S. A meta-analysis of the association between angiotensin-converting enzyme insertion/deletion gene polymorphism and the risk of overweight/obesity. J Renin Angiotensin Aldosterone Syst 2015; 16 (3): 687–94.
25. Pacholczyk M, Ferenc T, Kowalski J et al. Association of angiotensin-converting enzyme and angiotensin II type I receptor gene polymorphisms with extreme obesity in Polish individuals. DNA Cell Biol 2013; 32 (8): 435–42.
26. Das M, Pal S, Ghosh A. Synergistic effects of ACE (I/D) and Apo E (Hha I) gene polymorphisms on obesity, fat mass, and blood glucose level among the adult Asian Indians: A population-based study from Calcutta, India. Indian J Endocrinol Metab 2013; 17 (1): 101–4.
27. Kim K. Association of angiotensin-converting enzyme insertion/deletion polymorphism with obesity, cardiovascular risk factors and exercise-mediated changes in Korean women. Eur J Appl Physiol 2009; 105 (6): 879–87.
28. Suchánek P, Hubácek JA, Králová Lesná I et al. Actigenetic of ACE gene polymo-rphism in Czech obese sedentary females. Physiol Res 2009; 58 (Suppl. 1): S47–52.
29. Suzuki N, Matsunaga T, Nagasumi K et al. Alpha(2B)-adrenergic receptor deletion polymorphism associates with autonomic nervous system activity in young healthy Japanese. J Clin Endocrinol Metab 2003; 88 (3): 1184–7.
30. Fava C, Montagnana M, Guerriero M et al. Chromosome 2q12, the ADRA2B I/D polymorphism and metabolic syndrome. J Hypertens 2009; 27 (9): 1794–803.
31. Etzel JP, Rana BK, Wen G et al. Genetic variation at the human alpha2B-adrenergic receptor locus: role in blood pressure variation and yohimbine response. Hypertension 2005; 45 (6): 1207–13.
32. Laukkanen JA, Mäkikallio TH, Kauhanen J, Kurl S. Insertion/deletion polymor-phism in alpha2-adrenergic receptor gene is a genetic risk factor for sudden cardiac death. Am Heart J 2009; 158 (4): 615–21.
33. Zhang H, Li X, Huang J et al. Cardiovascular and metabolic phenotypes in relation to the ADRA2B insertion/deletion polymorphism in a Chinese population. J Hypertens 2005; 23 (12): 2201–7.
34. Papanas N, Papatheodorou K, Papazoglou D et al. An insertion/deletion polymorphism in the alpha2B adrenoceptor gene is associated with peripheral neuropathy in patients with type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes 2007; 115 (5): 327–30.
35. Sykiotis GP, Polyzogopoulou E, Georgopoulos NA et al. The alpha2B adrenergic receptor deletion/insertion polymorphism in morbid obesity. Clin Auton Res 2003; 13 (3): 203–7.
36. Vasudevan R, Ismail P, Stanslas J et al. Association of insertion/deletion polymorphism of alpha-adrenoceptor gene in essential hypertension with or without type 2 diabetes mellitus in Malaysian subjects. Int J Biol Sci 2008; 4 (6): 362–7.
37. Dionne IJ, Garant MJ, Nolan AA et al. Association between obesity and a polymorphism in the beta(1)-adrenoceptor gene (Gly389Arg ADRB1) in Caucasian women. Int J Obes Relat Metab Dis 2002; 26 (5): 633–9.
38. Linné Y, Dahlman I, Hoffstedt J. Beta1-Adrenoceptor gene polymorphism predicts long-term changes in body weight. Int J Obes (Lond) 2005; 29 (5): 458–62.
39. Voevoda M.I., Maksimov V.N., Kulikov I.V. Sudden cardi ac death and polymorphism of candidate genes for cardiovascular disease MEA. Novosibirsk, 2006; p. 23–7. [in Russian]
40. Mottagui-Tabar S, Hoffstedt J, Brookes AJ et al. Association of ADRB1 and UCP3 gene polymorphisms with insulin sensitivity but not obesity. Horm Res 2008; 69 (1): 31–6.
41. Gjesing AP, Andersen G, Albrechtsen A et al. Studies of associations between the Arg389Gly polymorphism of the beta1-adrenergic receptor gene (ADRB1) and hypertension and obesity in 7677 Danish white subjects. Diabet Med 2007; 24(4): 392–7.
42. Terra SG, McGorray SP, Wu R et al. Association between beta-adrenergic receptor polymorphisms and their G-protein-coupled receptors with body mass index and obesity in women: a report from the NHLBI-sponsored WISE study. Int J Obes (Lond) 2005; 29 (7): 746–54.
43. Souza-Costa DC, Belo VA, Silva PS et al. eNOS haplotype associated with hypertension in obese children and adolescents. Int J Obes (Lond) 2011; 35 (3): 387–92.
44. Hoffmann IS, Tavares-Mordwinkin R, Castejon AM et al. Endothelial nitric oxide synthase polymorphism, nitric oxide production, salt sensitivity and cardiovascular risk factors in Hispanics. J Hum Hypertens 2005; 19 (3): 233–40.
45. Miranda JA, Belo VA, Souza-Costa DC et al. eNOS polymorphism associated with metabolic syndrome in children and adolescents. Mol Cell Biochem 2013; 372 (1–2): 155–60.
46. Kucukhuseyin O, Kurnaz O, Akadam-Teker AB et al. The association of MTHFR C677T gene variants and lipid profiles or body mass index in patients with diabetic and nondiabetic coronary heart disease. J Clin Lab Anal 2013; 27 (6): 427–34.
47. Yang B, Fan S, Zhi X et al. Associations of MTHFR C677T and MTRR A66G gene polymorphisms with metabolic syndrome: a case-control study in Northern China. Int J Mol Sci 2014; 15 (12): 21687–702.
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Авторы
Т.А.Мулерова*1,2, Д.П.Цыганкова1, Е.Н.Воропаева3, В.Н.Максимов3, М.Ю.Огарков1,2
1 ФГБНУ НИИ комплексных проблем сердечно-сосудистых заболеваний. 650002, Россия, Кемерово, Сосновый б-р, д. 6;
2 ГБОУ ДПО Новокузнецкий государственный институт усовершенствования врачей Минздрава России. 654005, Россия, Новокузнецк, пр-т Строителей, д. 5;
3 ФГБНУ НИИ терапии и профилактической медицины. 630089, Россия, Новосибирск, ул. Бориса Богаткова, д. 175/1
*mulerova-77@mail.ru
1 Research Institute for Complex Issues of Cardiovascular Diseases. 650002, Russian Federation, Kemerovo, Sosnovii b-r, d. 6;
2 Novokuznetsk State Institute of Postgraduate Medicine of the Ministry of Health of the Russian Federation. 654005, Russian Federation, Novokuznetsk, pr-t Stroitelei, d. 5;
3 Institution of Internal and Preventive Medicine. 630089, Russian Federation, Novosibirsk, ul. Borisa Bogatkova, d. 175/1
*mulerova-77@mail.ru
1 ФГБНУ НИИ комплексных проблем сердечно-сосудистых заболеваний. 650002, Россия, Кемерово, Сосновый б-р, д. 6;
2 ГБОУ ДПО Новокузнецкий государственный институт усовершенствования врачей Минздрава России. 654005, Россия, Новокузнецк, пр-т Строителей, д. 5;
3 ФГБНУ НИИ терапии и профилактической медицины. 630089, Россия, Новосибирск, ул. Бориса Богаткова, д. 175/1
*mulerova-77@mail.ru
________________________________________________
1 Research Institute for Complex Issues of Cardiovascular Diseases. 650002, Russian Federation, Kemerovo, Sosnovii b-r, d. 6;
2 Novokuznetsk State Institute of Postgraduate Medicine of the Ministry of Health of the Russian Federation. 654005, Russian Federation, Novokuznetsk, pr-t Stroitelei, d. 5;
3 Institution of Internal and Preventive Medicine. 630089, Russian Federation, Novosibirsk, ul. Borisa Bogatkova, d. 175/1
*mulerova-77@mail.ru
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