Ассоциация генов бета-адренорецепторов, коннексина-40 и калиевого канала kcnh2с гипертрофией миокарда левого желудочка у больных гипертонической болезнью
Гипертоническая болезнь
Дата публикации: декабря 19, 2014
Ключевые слова
гипертрофия миокарда
гипертоническая болезнь
гипертоническая болезнь
Как цитировать
Минушкина Л., Горшкова Е., Бровкин А., Бражник В., Носиков В., Затейщиков Д. Ассоциация генов бета-адренорецепторов, коннексина-40 и калиевого канала kcnh2с гипертрофией миокарда левого желудочка у больных гипертонической болезнью // КРЕМЛЕВСКАЯ МЕДИЦИНА<br><i>клинический вестник</i>. 2014. Т. № 2. С. 26-30.
Аннотация
Целью нашего исследования было изучить ассоциацию полиморфных маркеров генах коннексина 40 (CX40)потенциал-зависимого калиевого канала (KCNH2), бета-адренорецепторов 1, 2 и 3 типа (ADRB1, ADRB2, ADRB3) соструктурными и функциональными особенностями миокарда левого желудочка у больных гипертонической болезнью.Обследовано 177 больных гипертонической болезнью (83 (46,9%) мужчины и 94 (53,1%) женщины). Среднийвозраст – 60,6±0,76 лет. В обследованной группе было 19 (10,9%) больных с АГ I степени, 57 (32,8%) больных с АГII степени и 101 (56,3%) – с АГ III степени. Структурные особенности миокарда левого желудочка исследовались спомощью эхокардиографии.В обследованной группе оказалось 55 больных без признаков ГЛЖ и 122 больных с увеличением ИММЛЖ.Больные с гипертрофией миокарда ЛЖ были старше (62,8±0,88 лет и 52,9±1,49 лет соотв., р = 0,001), имели большуюдлительность ГБ (16,0±1,07 лет и 10,7±1,44 лет, р = 0,018), более высокий уровень систолического АД (202,7±2,51мм.рт.ст. и 181,6±3,79 мм.рт.ст., р = 0,008) и больший индекс массы тела (29,4±0,41 кг/м2 и 26,6±0,57 кг/м2 , р =0,001). Среди больных с ГЛЖ было больше женщин (57,7% и 37,5%, р = 0,025) и больше больных с сахарным диабетомтипа 2 (17,5% и 5,0%, р = 0,040).Достоверные различия в частотах генотипов изученных генов-кандидатов были выявлены для полиморфногомаркера Gly389Arg гена ADRB1 – в группе больных с ГЛЖ частота генотипа Arg/Arg была достоверно выше, чем средибольных без ГЛЖ (OR 2,32 [1,34–4,11]). В группе больных с ГЛЖ частота генотипа Thrк/Thr полиморфного маркераLys897Thr в гене KCNH2 была достоверно выше (OR 5.35[1.50–19.12]), чем среди больных без ГЛЖ.Ключевые слова: гипертрофия миокарда, гипертоническая болезнь.The purpose of our trial was to study association of polymorphous markers of genes Connexin-40 (CX40) potential-dependentpotassium channel (KCNH2), b-adrenoreceptors of types 1, 2 and 3 (ADRB1, ADRB2, ADRB3) with structural andfunctional peculiarities of left myocardial ventricle in patients with hypertensive disease.177 patients with hypertensive disease (83 (46.9%) men and 94 (53.1%)women) were examined. Average agewas 60.6±0.76. In the study group there were 19 (10.9%) patients with arterial hypertension (AH) of stage I, 57 (32.8%)patients with AH stage II and 101 (56.3%) patients with AH stage III. Structural peculiarities of the left myocardial ventriclewere studied with echocardiography.In the study group there were 55 patients without hypertrophy of the left ventricle (HLV) and 122 patients with the increasedmass index of the left ventricle. Patients with hypertrophy of left myocardial ventricle were older (62.8±0.88 years oldand 52.9±1.49 years old, correspondingly, р = 0.001); they had longer history of hypertensive disease (16.0±1.07years and10.7±1.44 years, р = 0.018), higher level of systolic AP (202.7±2.51 mm Hg and 181.6±3.79 mm Hg, р = 0.008) and largerbody weight index (29.4±0.41 kg/m2 and 26.6±0.57 kg/m2 , р = 0.001). Women were more numerous among patients withHVL (57.7% and 37.5%, р = 0.025 and among patients with diabetes mellitus 2 (17.5% and 5.0%, р = 0.040).Reliable differences in occurrence of gene types of the studied gene-candidates were found out for polymorphous markerGly389Arg of gene ADRB1 – in patients with HVL occurrence of genotype Arg/Arg was reliably higher than among patientswithout HLV (OR 2.32 [1.34–4.11]). In the group of patients with HVL occurrence of genotype Thrк/Thr of polymorphousmarkers Lys897Thr in gene KCNH2 was reliably higher (OR 5.35[1.50–19.12]) than among patients without HVL.Key words: myocardial hypertrophy, hypertensive disease.Литература
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(2). – P. 507–511.
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in individuals at risk of coronary events. A WOSCOPS substudy.
Eur. Heart J. – 2002. – Vol. 23 (14). – P. 1087–1092.
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adrenergic receptor gene polymorphisms with left ventricular
hypertrophy in human essential hypertension. Clin. Biochem. –
2008. – Vol. 41 (10–11). – P. 773–778.
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variations associated with echocardiographic left ventricular traits
in hypertensive blacks. Hypertension. – 2007. – Vol. 49 (5). – P.
992–999.
10. Karlsson J., Lind L., Hallberg P. и др. Beta1-adrenergic
receptor gene polymorphisms and response to beta1-adrenergic
receptor blockade in patients with essential hypertension. Clin
Cardiol. – 2004. – Vol. 27 (6). – P. 347–350.
11. Canham R.M., Das S.R., Leonard D. и др.
{alpha}2cDel322–325 and {beta}1Arg389 Adrenergic Polymorphisms
Are Not Associated With Reduced Left Ventricular Ejection Fraction
or Increased Left Ventricular Volume. J Am Coll Cardiol. – 2007.
– Vol. 49 (2). – P. 274–276.
12. Woodiwiss A.J., Badenhorst D., Sliwa K. и др. Beta1- and
alpha2c-adrenoreceptor variants as predictors of clinical aspects of
dilated cardiomyopathy in people of African ancestry. Cardiovasc J
Afr. – 2008. – Vol. 19 (4). – P. 188–193.
13. Iaccarino G., Lanni F., Cipolletta E. и др. The Glu27
allele of the beta2 adrenergic receptor increases the risk of cardiac
hypertrophy in hypertension. J. Hypertens. – 2004. – Vol. 22 (11).
– P. 2117–2122.
14. Elbein S.C., Hoffman M., Barrett K. и др. Role of the beta
3-adrenergic receptor locus in obesity and noninsulin-dependent
diabetes among members of Caucasian families with a diabetic
sibling pair. J. Clin. Endocrinol. Metab. – 1996. – Vol. 81 (12).
– P. 4422–4427.
15. Barbier J., Rannou-Bekono F., Marchais J., Tanguy S.,
Carr F. Alterations of beta3-adrenoceptors expression and their
myocardial functional effects in physiological model of chronic
exercise-induced cardiac hypertrophy. Mol. Cell. Biochem. – 2007.
– Vol. 300 (1–2). – P. 69–75
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J. – 2004. – Vol. 25 (22). – P. 1979–1989.
17. Kirchhoff S., Kim J.S., Hagendorff A., Thnnissen E. et al.
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connexin43 double-deficient mice. Circ Res. – 2000. – Vol. 1;87(5).
– P. 399–405.
18. Bierhuizen M.F., Boulaksil M., van Stuijvenberg L. et al.
In calcineurin-induced cardiac hypertrophy expression of Nav1.5,
Cx40 and Cx43 is reduced by different mechanisms. J Mol Cell
Cardiol. – 2008. – Vol. 45 (3). – P. 373–184.
19. Bastide B., Neyses L., Ganten D. et al. Gap junction protein
connexin40 is preferentially expressed in vascular endothelium
and conductive bundles of rat myocardium and is increased under
hypertensive conditions. Circ Res. – 1993. – Vol. 73 (6). – P.
1138–1149.
20. Song Y.N., Zhang H., Zhao J.Y., Guo X.L.Connexin 43,
a new therapeutic target for cardiovascular diseases. Pharmazie.
– 2009. – Vol. 64 (5). – P. 291–295.
21. Firouzi M., Bierhuizen M.F., Kok B. et al. The human
Cx40 promoter polymorphism -44G-->A differentially affects
transcriptional regulation by Sp1 and GATA4. Biochim Biophys
Acta. – 2006. – Vol. 1759 (10). – P. 491–496.
22. Juang J.M., Chern Y.R., Tsai C.T. et al. The association
of human connexin 40 genetic polymorphisms with atrial fibrillation.
Int J Cardiol. – 2007. – Vol. 2;116(1). – P. 107–112.
23. Hauer R.N., Groenewegen W.A., Firouzi M. et al. Cx40
polymorphism in human atrial fibrillation. Adv Cardiol. – 2006.
– Vol. 42. – P. 284–291.
24. Wang Y.H., Shi C.X., Dong F. et al. Inhibition of the rapid
component of the delayed rectifier potassium current in ventricular
myocytes by angiotensin II via the AT1 receptor. Br J Pharmacol.
– 2008. – Vol. 154 (2). – P. 429–439.
25. Sauviat M.P., Pages N. Cardiotoxicity of lindane, a gamma
isomer of hexachlorocyclohexane J Soc Biol. – 2002. – Vol. 196 (4).
– P. 339–348.
Laragh J.H. Relation of left ventricular mass and geometry to
morbidity and mortality in uncomplicated essential hypertension.
Ann. Intern. Med. – 1991. – Vol. 114 (5). – P. 345–352.
2. Mosterd A., D’Agostino R.B., Silbershatz H. и др. Trends
in the prevalence of hypertension, antihypertensive therapy, and
left ventricular hypertrophy from 1950 to 1989. N. Engl. J. Med.
– 1999. – Vol. 340 (16). – P. 1221–1227.
3. Devereux R.B., Reichek N. Echocardiographic
determination of left ventricular mass in man. Anatomic validation
of the method. Circulation. – 1977. – Vol. 55 (4). – P. 613–618.
4. Noori S., Friedlich P., Seri I. Developmentally Regulated
Cardiovascular, Renal, and Neuroendocrine Effects of Dopamine
NeoReviews. – 2003. – Vol. 4, No.10. – P. e28.
5. Ranade K., Jorgenson E., Sheu W.H. и др. A polymorphism
in the beta1 adrenergic receptor is associated with resting heart rate.
Am. J. Hum. Genet. – 2002. – Vol. 70 (4). – P. 935–942.
6. Nieminen T., Lehtimki T., Laiho J., и др. Effects of
polymorphisms in beta1-adrenoceptor and alpha-subunit of G
protein on heart rate and blood pressure during exercise test. The
Finnish Cardiovascular Study. J. Appl. Physiol. – 2006. – Vol. 100
(2). – P. 507–511.
7. White H.L., Maqbool A., McMahon A.D. и др. An
evaluation of the beta-1 adrenergic receptor Arg389Gly polymorphism
in individuals at risk of coronary events. A WOSCOPS substudy.
Eur. Heart J. – 2002. – Vol. 23 (14). – P. 1087–1092.
8. Fu C., Wang H., Wang S. и др. Association of beta 1-
adrenergic receptor gene polymorphisms with left ventricular
hypertrophy in human essential hypertension. Clin. Biochem. –
2008. – Vol. 41 (10–11). – P. 773–778.
9. Meyers K.J., Mosley T.H., Fox E. и др. Genetic
variations associated with echocardiographic left ventricular traits
in hypertensive blacks. Hypertension. – 2007. – Vol. 49 (5). – P.
992–999.
10. Karlsson J., Lind L., Hallberg P. и др. Beta1-adrenergic
receptor gene polymorphisms and response to beta1-adrenergic
receptor blockade in patients with essential hypertension. Clin
Cardiol. – 2004. – Vol. 27 (6). – P. 347–350.
11. Canham R.M., Das S.R., Leonard D. и др.
{alpha}2cDel322–325 and {beta}1Arg389 Adrenergic Polymorphisms
Are Not Associated With Reduced Left Ventricular Ejection Fraction
or Increased Left Ventricular Volume. J Am Coll Cardiol. – 2007.
– Vol. 49 (2). – P. 274–276.
12. Woodiwiss A.J., Badenhorst D., Sliwa K. и др. Beta1- and
alpha2c-adrenoreceptor variants as predictors of clinical aspects of
dilated cardiomyopathy in people of African ancestry. Cardiovasc J
Afr. – 2008. – Vol. 19 (4). – P. 188–193.
13. Iaccarino G., Lanni F., Cipolletta E. и др. The Glu27
allele of the beta2 adrenergic receptor increases the risk of cardiac
hypertrophy in hypertension. J. Hypertens. – 2004. – Vol. 22 (11).
– P. 2117–2122.
14. Elbein S.C., Hoffman M., Barrett K. и др. Role of the beta
3-adrenergic receptor locus in obesity and noninsulin-dependent
diabetes among members of Caucasian families with a diabetic
sibling pair. J. Clin. Endocrinol. Metab. – 1996. – Vol. 81 (12).
– P. 4422–4427.
15. Barbier J., Rannou-Bekono F., Marchais J., Tanguy S.,
Carr F. Alterations of beta3-adrenoceptors expression and their
myocardial functional effects in physiological model of chronic
exercise-induced cardiac hypertrophy. Mol. Cell. Biochem. – 2007.
– Vol. 300 (1–2). – P. 69–75
16. Teunissen B.E., Jongsma H.J., Bierhuizen M.F. Regulation
of myocardial connexins during hypertrophic remodelling. Eur Heart
J. – 2004. – Vol. 25 (22). – P. 1979–1989.
17. Kirchhoff S., Kim J.S., Hagendorff A., Thnnissen E. et al.
Abnormal cardiac conduction and morphogenesis in connexin40 and
connexin43 double-deficient mice. Circ Res. – 2000. – Vol. 1;87(5).
– P. 399–405.
18. Bierhuizen M.F., Boulaksil M., van Stuijvenberg L. et al.
In calcineurin-induced cardiac hypertrophy expression of Nav1.5,
Cx40 and Cx43 is reduced by different mechanisms. J Mol Cell
Cardiol. – 2008. – Vol. 45 (3). – P. 373–184.
19. Bastide B., Neyses L., Ganten D. et al. Gap junction protein
connexin40 is preferentially expressed in vascular endothelium
and conductive bundles of rat myocardium and is increased under
hypertensive conditions. Circ Res. – 1993. – Vol. 73 (6). – P.
1138–1149.
20. Song Y.N., Zhang H., Zhao J.Y., Guo X.L.Connexin 43,
a new therapeutic target for cardiovascular diseases. Pharmazie.
– 2009. – Vol. 64 (5). – P. 291–295.
21. Firouzi M., Bierhuizen M.F., Kok B. et al. The human
Cx40 promoter polymorphism -44G-->A differentially affects
transcriptional regulation by Sp1 and GATA4. Biochim Biophys
Acta. – 2006. – Vol. 1759 (10). – P. 491–496.
22. Juang J.M., Chern Y.R., Tsai C.T. et al. The association
of human connexin 40 genetic polymorphisms with atrial fibrillation.
Int J Cardiol. – 2007. – Vol. 2;116(1). – P. 107–112.
23. Hauer R.N., Groenewegen W.A., Firouzi M. et al. Cx40
polymorphism in human atrial fibrillation. Adv Cardiol. – 2006.
– Vol. 42. – P. 284–291.
24. Wang Y.H., Shi C.X., Dong F. et al. Inhibition of the rapid
component of the delayed rectifier potassium current in ventricular
myocytes by angiotensin II via the AT1 receptor. Br J Pharmacol.
– 2008. – Vol. 154 (2). – P. 429–439.
25. Sauviat M.P., Pages N. Cardiotoxicity of lindane, a gamma
isomer of hexachlorocyclohexane J Soc Biol. – 2002. – Vol. 196 (4).
– P. 339–348.