**3. Conclusion**

**Genotypes**

**Patients with secondary atrial fibrillation N= 61**

72 Atrial Fibrillation - Mechanisms and Treatment

healthy relatives and persons of the control group.

55,70%

relatives and persons of the control group.

healthy relatives and persons of the control group.

0% 10% 20% 30% 40% 50% 60% 70%

fibrillation [42, 44].

**3. Conclusion** 

rial fibrillation.

susceptibility.

**4. Acknowledgment**

**5. References** 

44,4%

P1-3>0,05

**%**

**Absolute value**

**Healthy relatives N=144**

**%**

**Absolute value**

Note: Differences in the investigated parameters were calculated using the χ2 criterion.

39,6% 44,30%

*Note: Differences in the investigated parameters were calculated using the χ2 criterion.* 

kinases synthesis, all these factors contributing to the development of atrial fibrillation.

intracellular signaling (e.g. migration of the Са from intracellular stores to the cytosol).

primary atrial fibrillation (62,2%) as compared with the control group (39,6%) is shown.

conduction system, thereby contributing to the development of atrial fibrillation [45].

for their help in genetic testing and their continued support and assistance in our investigations.

[1] Diagnostika i lechenie fibrilljacii predserdij: Rossiyskie rekomendatsii. Terapevt 2005;(1/2) 11-37.

We studied the eNOS 894 G/T polymorphism in the group of patients described above.

polymorphisms combinations, which are likely to cause the development of atrial fibrillation seems to be necessary.

ранняя диагностика, specific atrial fibrillation preventive care as well as on-time treatment of this type of arrhythmia.

(44,4%) as compared with the control group (25,3%) is established.

risk group for the development of this pathology.

**Control group N=91**

**%**

0,00%

3,50% 9,90%

**Absolute value**

G/G 34 55,7±6,4 64 44,4±4,1 36 39,6±5,1 р>0,05 р>0,05 р>0,05 G/T 27 44,3±6,4 75 52,1±4,2 46 50,5±5,2 р>0,05 р>0,05 р>0,05 T/T 0 0 5 3,5±1,5 9 9,9±3,1 р>0,05 Р>0,05 р>0,05

**Table 9.** Genotype frequency of the eNOS 894 G/T polymorphism in patients with secondary atrial fibrillation, their

52,10% 50,50%

GG GT TT 1 Patients with secondary atrial fibrillation (n=61) 2 Healthy relatives (n=144) 3 Control group (n=91)

Figure 6. Genotype frequency of the eNOS 894 G/T polymorphism in patients with secondary atrial fibrillation, their healthy

**Figure 6.** Genotype frequency of the eNOS 894 G/T polymorphism in patients with secondary atrial fibrillation, their

As was mentioned above, the decrease in the production of NO-synthase can cause oxida‐ tive stress, lead to disturbances in cardiac conduction system and provoke the re-entry mechanism in the atria, thereby contributing to the development of atrial fibrillation [42, 44].

The investigated genetic markers may be used in diagnosing of primary atrial fibrillation susceptibility.

This paper demonstrates a significant prevalence of homozygous genotype G/G of the endo‐ thelial NO synthase (eNOS) gene in patients with primary atrial fibrillation. Specifically, polymorphism of the endothelial NO synthase (eNOS) gene causes the decrease in the level of NO and calcium in the cells as well as disturbances in the physiological process of HMFdependent protein kinases synthesis, all these factors contributing to the development of at‐

The investigated genetic markers may be used in diagnosing of primary atrial fibrillation

As was mentioned above, the decrease in the production of NO-synthase can cause oxidative stress, lead to disturbances in cardiac conduction system and provoke the re-entry mechanism in the atria, thereby contributing to the development of atrial

This paper demonstrates a significant prevalence of homozygous genotype G/G of the endothelial NO synthase (eNOS) gene in patients with primary atrial fibrillation. Specifically, polymorphism of the endothelial NO synthase (eNOS) gene causes the decrease in the level of NO and calcium in the cells as well as disturbances in the physiological process of HMF-dependent protein

A significant prevalence of homozygous genotype I/I of the gene ADRA2B in patients with primary atrial fibrillation

 The relatives of the probands with primary atrial fibrillation and homozygous genotype I/I can be subsumed under the risk group for the development of this pathology. Changes in the aminoacid profile of the third intracellular loop of the α2ß- adrenergic receptor due to the polymorphism I/I of the ADRA2B gene disturb the interaction of the receptor with effector proteins (G-protein or receptor protein kinase), which cause changes in receptor activity autoregulation or associated with the activity cАМP processes of

A significant prevalence of homozygous genotype G/G of the endothelial NO synthase (eNOS) gene in patients with

The relatives of the probands with primary atrial fibrillation and homozygous genotype G/G can be subsumed under the

A certain role in atrial fibrillation pathogenesis can be played by nitrogen oxide molecules (NO). Nitrogen oxide is constantly produced in the human organism enzymatically from L – arginine and performs a function of a universal messenger in intracellular signaling [19]. NO synthase (NOS, EC number 1.14.13.39) is a catalyst in this reaction [19]. Under the influence of NOS L – arginine oxidation and nitrogen oxide synthesis takes place in vessel endotheliocytes. Then, going from the endotheliocytes to the smooth muscle cells, NO labilizes soluble guanylate cyclase, thereby contributing to the decrease in the level of the rhythmic hydroxymethylfurfurol (HMF), activation of the rhythmic HMF – dependent protein kinases, changes in Ca concentration, susceptibility of the conducting cardiac myocytes receptors to the level of catecholamines. In case of polymorphism G/G of the endothelial NO synthase (eNOS) gene the level of nitrogen oxide and intracellular Ca decreases, the physiological process of HMF-dependent protein kinases synthesis is disturbed, which contributes to the development of heart rhythm disorders.

As was mentioned above, the decrease in the production of NO-synthase can cause oxidative stress and changes in cardiac

Continuing the search of candidate genes of the primary and secondary atrial fibrillation and the study of different genes

The final result of these investigations can be genetic identification of the atrial fibrillation risk groups, early diagnostics,

We would like to thank Mikhail Voevoda, Vladimir Maksimov and staff of the Research Institute of Therapy, Novosibirsk, Russia

**р1-2 р1-3 р2-3**

A significant prevalence of homozygous genotype I/I of the gene ADRA2B in patients with primary atrial fibrillation (44,4%) as compared with the control group (25,3%) is established.

The relatives of the probands with primary atrial fibrillation and homozygous genotype I/I can be subsumed under the risk group for the development of this pathology. Changes in the aminoacid profile of the third intracellular loop of the α2ß- adrenergic receptor due to the polymorphism I/I of the ADRA2B gene disturb the interaction of the receptor with effec‐ tor proteins (G-protein or receptor protein kinase), which cause changes in receptor activity autoregulation or associated with the activity cАМP processes of intracellular signaling (e.g. migration of the Са from intracellular stores to the cytosol).

A significant prevalence of homozygous genotype G/G of the endothelial NO synthase (eNOS) gene in patients with primary atrial fibrillation (62,2%) as compared with the control group (39,6%) is shown.

The relatives of the probands with primary atrial fibrillation and homozygous genotype G/G can be subsumed under the risk group for the development of this pathology.

A certain role in atrial fibrillation pathogenesis can be played by nitrogen oxide molecules (NO). Nitrogen oxide is constantly produced in the human organism enzymatically from L – arginine and performs a function of a universal messenger in intracellular signaling [19]. NO synthase (NOS, EC number 1.14.13.39) is a catalyst in this reaction [19]. Under the influ‐ ence of NOS L – arginine oxidation and nitrogen oxide synthesis takes place in vessel endo‐ theliocytes. Then, going from the endotheliocytes to the smooth muscle cells, NO labilizes soluble guanylate cyclase, thereby contributing to the decrease in the level of the rhythmic hydroxymethylfurfurol (HMF), activation of the rhythmic HMF – dependent protein kinas‐ es, changes in Ca concentration, susceptibility of the conducting cardiac myocytes receptors to the level of catecholamines. In case of polymorphism G/G of the endothelial NO synthase (eNOS) gene the level of nitrogen oxide and intracellular Ca decreases, the physiological process of HMF-dependent protein kinases synthesis is disturbed, which contributes to the development of heart rhythm disorders.

We studied the eNOS 894 G/T polymorphism in the group of patients described above.

As was mentioned above, the decrease in the production of NO-synthase can cause oxida‐ tive stress and changes in cardiac conduction system, thereby contributing to the develop‐ ment of atrial fibrillation [45].

Continuing the search of candidate genes of the primary and secondary atrial fibrillation and the study of different genes polymorphisms combinations, which are likely to cause the development of atrial fibrillation seems to be necessary.

The final result of these investigations can be genetic identification of the atrial fibrillation risk groups, early diagnostics, ранняя диагностика, specific atrial fibrillation preventive care as well as on-time treatment of this type of arrhythmia.

Acknowledgment We would like to thank Mikhail Voevoda, Vladimir Maksimov and staff of the Research Institute of Therapy, Novosibirsk, Russia for their help in genetic testing and their continued support and assistance in our investigations.

[10] Roberts DJ., Michael H., Gollob M.H. Impact of genetic discoveries on the classifica‐

New Candidate Genes in Atrial Fibrillation Polymorphisms of the Alpha 2-Beta-Adrenoceptor and the Endothelial…

http://dx.doi.org/10.5772/53527

75

[11] Bharati S., Surawicz B., Vidaillet HJ. Familial congenital sinus rhythm anomalies:

[13] Lomasney JW., Lorenz W., Allen LF. et al. Expansion of the α2-Adrenergic Receptor Family: Cloning and characterization of a human α2-adrenergic receptor subtype, the gene for which is located on chromosome 2. Proc. Natl. Acad. Sci. USA 1990; 87

[14] Hein L., Altman JD., Kobilka BK. Two functionally distinct alpha2-adrenergic recep‐ tors regulate sympathetic neurotransmission. Nature 1999; 402 (6758) 181-184. [15] Wowern F., Bengtsson K., Lindblad U. et al. Functional variant in the (alpha)2B adre‐ noceptor gene, a positional candidate on chromosome 2, associates with hyperten‐

[16] Hjalmarson A. Heart rate and beta-adrenergic mechanisms in acute myocardial in‐

[17] Koch WJ., Lefkowitz J., Rockman HA. Functional consequences of altering myocar‐

[18] Coumel P. Neurogenic and humoral influences of the autonomic nervous system in the determination of paroxysmal atrial fibrillation. The аtrium in health and disease.

[19] Pokrovsky VI. Oksid azota, ego fiziologicheskie i patofiziologicheskie svoystva. Tera‐

[20] Kim M. Myocardial Nox2 containing NAD(P)H oxidase contributes to oxidative.

[23] Tikanoja T. Familial atrial fibrillation with fetal onset. Jpn. Heart J 1998; 79 (2)

[25] Zharko KP. O semeynyh formah narusheniya ritma serdtsa i provodimosti. Vracheb.

[26] Zav'yalov AI., Zav'yalov DA. Serdtse i myshechnaya rabota. Aktual'nye voprosy bio‐ medicinskoy i klinicheskoy antropologii: mater. konf. Krasnoyarsk 1997 35-36. [27] Poret P., Mabo P., Deplace C. Is isolated atrial fibrillation genetically determined? Apropos of a familial history. Arch. Mol. Coeur. Vaiss 1996;89(9) 1197-1203.

Stress in human atrial fibrillation. Circ. Res 2005; 97 629-636.

[22] Dzyak VN. Mercatel'naya aritmiya. Kiev: Zdorovye; 1979.

[24] Boitsov SA. Mercatel'naya aritmiya. SPb: ELBI; 2001.

[21] Wolf L. Familial auricular fibrillation. N. Engl. J. Med.; 1943. p396-397.

dial adrenergic receptor signaling. Annu. Rev. Physiol 2000; 62 237-260.

tion of lone atrial fibrillation. J. Am. Coll. Cardiol 2010;55(8) 705-711.

clinical and pathological correlations. PACE 1992; 15 (Pt. 1) 1720-1729.

[12] Wolf L. Familial auricular fibrillation. N. Engl. J. Med 1943; 229 396-397.

(13) 5094-5098.

sion. Hypertension 2004;43(3) 231-233.

N. Y.: Futura Publ. Co.; 1982. p213-232.

pevt. Arhiv. 2005;1 82-87.

195-197.

delo 1981;7 67-68.

farction. Basic Res. Cardiol 1990; 85 325-333.
