**2.3. Polymorphism of the endothelial NO synthase (eNOS) gene in probands with atrial fibrillation, their healthy relatives and persons of the control group**

In our work we investigated polymorphisms of the endothelial NO synthase (eNOS) gene in patients with atrial fibrillation, their healthy relatives and persons from the control group. According to the results of PCR in patients with atrial fibrillation, their healthy relatives and persons from the control group three sorts of NO synthase genotypes were revealed: G/G – homozygous, G/T – heterozygous, T/T – homozygous.

Homozygous genotype (894 G/G) of the endothelial NO synthase (eNOS) gene in patients with atrial fibrillation was revealed in 58,5±4,8% (62 persons), heterozygous genotype (894 G/T) – in 39,6±4,8% (42 persons). Homozygous genotype in a rare allele (894 T/T) was geno‐ typed in 1,9±1,3% (2 persons) (Table 7).

Among the probands' healthy relatives genotypes appeared to be spread as follows: homo‐ zygous genotype (894 G/G) –in 44,4±4,1% (64 persons), heterozygous genotype (894 G/T) – in 52,1±4,2% (75 persons), homozygous genotype in a rare allele (894 T/T) –in 3,5±1,5% (5 persons) (Table 7). As for the control group, homozygous genotype (894 G/G) of the gene of endothelial NO synthase was revealed in 39,6±5,1% (36 persons), heterozygous genotype (894 G/T) – in 50,5±5,2% (46 persons). Homozygous genotype in a rare allele (894 T/T) was genotyped in 9,9±3,1% (9 persons) (Table 7).

A significant prevalence of homozygous genotype G/G in patients with atrial fibrillation (58,5%) as compared with the control group (39,6%) is established; the difference is statisti‐ cally reliable (р =0,039) (Table 7, Fig. 4).

Absolute value

persons of the control group.

**persons of the control group.** 


**2.3 Polymorphism of the endothelial NO synthase (eNOS) gene in probands with atrial fibrillation, their healthy relatives and** 

Therefore, summarizing the abovementioned, homozygous genotype I/I of the gene ADRА2В may be regarded as one of the genetic predictors of primary atrial fibrillation onset. The relatives of the probands with primary atrial fibrillation and homozygous genotype I/I compose a high risk group for the appearance of this disorder. The conducted research of the gene ADRА2В polymorphism in patients with primary and secondary atrial fibrillation, can contribute to the decision of the etiological

Note: Differences in the investigated parameters were calculated using the χ2 criterion. Genotype frequency of the eNOS 894 G/T polymorphism in patients with atrial fibrillation,

% Absolute

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

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

**Table 7.** Genotype frequency of the eNOS 894 G/T polymorphism in patients with atrial fibrillation, their healthy relatives and persons of the control group. Genotypes Patients with atrial fibrillation N= 106 Healthy relatives N=144 Control group N=91 р1-2 р1-3 р2-3

value % Absolute

their healthy relatives and persons of the control group.

G/G 62 58,5±4,8 64 44,4±4,1 36 39,6±5,1 р>0,05 р<0,05 р>0,05 G/T 42 39,6±4,8 75 52,1±4,2 46 50,5±5,2 р>0,05 р>0,05 р>0,05 T/T 2 1,9±1,3 5 3,5±1,5 9 9,9±3,1 р>0,05 Р<0,05 р>0,05

value %

**Genotyp es**

Genotypes

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

Genotypes

and persons of the control group.

rare allele (894 T/T) was not genotyped (Table 9).

healthy relatives and persons of the control group.

Patients with secondary atrial fibrillation N= 61

Absolute value

was not genotyped (Table 9).

**Patients with primary atrial fibrillation N= 45**

healthy relatives and persons of the control group.

62,20%

44,4%

Patients with primary atrial fibrillation N= 45

**Healthy relatives N=144**

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

T/T 2 4,4±3,1 5 3,5±1,5 9 9,9±3,1 р>0,05 Р>0,05 р>0,05

Genotype frequency of the eNOS 894 G/T polymorphism in patients with primary atrial fibrillation, their healthy relatives and persons of the control group.

**Table 8.** Genotype frequency of the eNOS 894 G/T polymorphism in patients with primary atrial fibrillation, their

G/G 28 62,2±7,2 64 44,4±4,1 36 39,6±5,1 р>0,05 р<0,05 р>0,05 G/T 15 33,3±7,0 75 52,1±4,2 46 50,5±5,2 р>0,05 р>0,05 р>0,05 T/T 2 4,4±3,1 5 3,5±1,5 9 9,9±3,1 р>0,05 Р>0,05 р>0,05

GG GT TT 1 Patients with primary atrial fibrillation (n=106) 2 Healthy relatives (n=144) 3 Control group (n=91)

Figure 5. Genotype frequency of the eNOS 894 G/T polymorphism in patients with primary atrial fibrillation, their healthy relatives

**Figure 5.** Genotype frequency of the eNOS 894 G/T polymorphism in patients with primary atrial fibrillation, their

In patients with secondary atrial fibrillation homozygous genotype (894 G/G) of the endo‐ thelial NO synthase (eNOS) gene was revealed in 55,7±6,4% (34 persons), heterozygous gen‐ otype (894 G/T) – in 44,3±6,4% (27 persons), homozygous genotype in a rare allele (894 T/T)

Genotype frequency of the eNOS 894 G/T polymorphism in patients with secondary atrial fibrillation, their healthy relatives and persons of the control group.

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

No significant differences were established between frequencies of genotypes of the endo‐ thelial NO synthase (eNOS) gene in patients with secondary atrial fibrillation, their healthy

in patients with secondary atrial fibrillation, their healthy relatives and persons of the control group (Table 9, Fig. 6).

value % Absolute

Healthy relatives N=144

% Absolute

relatives and persons of the control group (Table 9, Fig. 6).

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

In patients with secondary atrial fibrillation homozygous genotype (894 G/G) of the endothelial NO synthase (eNOS) gene was revealed in 55,7±6,4% (34 persons), heterozygous genotype (894 G/T) – in 44,3±6,4% (27 persons), homozygous genotype in a

No significant differences were established between frequencies of genotypes of the endothelial NO synthase (eNOS) gene

Control group N=91

value %

**Abs. % Abs. % Abs. %**

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

Абс. % Абс. % Абс. %

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

P1-3<0,05

39,6%

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

Healthy relatives N=144

33,30%

G/G 28 62,2±7,2 64 44,4±4,1 36

G/T 15 33,3±7,0 75 52,1±4,2 46

**Control group**

39,6±5,

50,5±5,

Control group

52,10% 50,50%

**N=91 <sup>р</sup>1-2 <sup>р</sup>1-3 <sup>р</sup>2-3**

<sup>1</sup> р>0,05 р<0,05 р>0,05

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71

<sup>2</sup> р>0,05 р>0,05 р>0,05

4,40% 3,50% 9,90%

р1-2 р1-3 р2-3

N=91 р1-2 р1-3 р2-3

Table 8

Table 9

was revealed in 62,2±7,2% (28 persons), heterozygous genotype (894 G/T) – in 33,3±7,0% (15 persons), homozygous genotype in a rare allele (894 T/T) was genotyped in 4,4±3,1% (2 persons) (Table 8). A significant prevalence of homozygous genotype G/G as compared with the control group is established only in patients **Figure 4.** Genotype frequency of the eNOS 894 G/T polymorphism in patients with atrial fibrillation, their healthy rela‐ tives and persons of the control group.

with primary atrial fibrillation, 62,2% и 39,6% respectively; the difference is statistically reliable (р =0,021) (Table 8, Fig. 5).

Figure 4. Genotype frequency of the eNOS 894 G/T polymorphism in patients with atrial fibrillation, their healthy relatives and

In patients with primary atrial fibrillation homozygous genotype (894 G/G) of the endothelial NO synthase (eNOS) gene

In patients with primary atrial fibrillation homozygous genotype (894 G/G) of the endothe‐ lial NO synthase (eNOS) gene was revealed in 62,2±7,2% (28 persons), heterozygous geno‐ type (894 G/T) – in 33,3±7,0% (15 persons), homozygous genotype in a rare allele (894 T/T) was genotyped in 4,4±3,1% (2 persons) (Table 8).

A significant prevalence of homozygous genotype G/G as compared with the control group is established only in patients with primary atrial fibrillation, 62,2% и 39,6% respectively; the difference is statistically reliable (р =0,021) (Table 8, Fig. 5).

New Candidate Genes in Atrial Fibrillation Polymorphisms of the Alpha 2-Beta-Adrenoceptor and the Endothelial… http://dx.doi.org/10.5772/53527 71


Note: Differences in the investigated parameters were calculated using the χ2 criterion. Genotype frequency of the eNOS 894 G/T polymorphism in patients with primary atrial fibrillation, their healthy relatives and persons of the control group.

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

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

Healthy relatives

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

and persons of the control group.

rare allele (894 T/T) was not genotyped (Table 9).

secondary atrial

Patients with primary atrial

**Genotypes**

Genotypes

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

persons of the control group.

tives and persons of the control group.

**Patients with atrial fibrillation N= 106**

**%**

allele (894 T/T) was genotyped in 1,9±1,3% (2 persons) (Table 7).

**Absolute value**

issue of hereditary atrial fibrillation.

70 Atrial Fibrillation - Mechanisms and Treatment

**persons of the control group.** 

heterozygous, T/T – homozygous.

relatives and persons of the control group.

Absolute value

58,50%

Patients with atrial fibrillation N= 106

**Healthy relatives N=144**

**%**

**Table 7.** Genotype frequency of the eNOS 894 G/T polymorphism in patients with atrial fibrillation, their healthy

value % Absolute

G/G 62 58,5±4,8 64 44,4±4,1 36 39,6±5,1 р>0,05 р<0,05 р>0,05 G/T 42 39,6±4,8 75 52,1±4,2 46 50,5±5,2 р>0,05 р>0,05 р>0,05 T/T 2 1,9±1,3 5 3,5±1,5 9 9,9±3,1 р>0,05 Р<0,05 р>0,05

GG GT TT 1 Patients with atrial fibrillation (n=106) 2 Healthy relatives (n=144) 3 Control group (n=91)

Figure 4. Genotype frequency of the eNOS 894 G/T polymorphism in patients with atrial fibrillation, their healthy relatives and

with primary atrial fibrillation, 62,2% и 39,6% respectively; the difference is statistically reliable (р =0,021) (Table 8, Fig. 5).

**Figure 4.** Genotype frequency of the eNOS 894 G/T polymorphism in patients with atrial fibrillation, their healthy rela‐

In patients with primary atrial fibrillation homozygous genotype (894 G/G) of the endothe‐ lial NO synthase (eNOS) gene was revealed in 62,2±7,2% (28 persons), heterozygous geno‐ type (894 G/T) – in 33,3±7,0% (15 persons), homozygous genotype in a rare allele (894 T/T)

A significant prevalence of homozygous genotype G/G as compared with the control group is established only in patients with primary atrial fibrillation, 62,2% и 39,6% respectively;

In patients with primary atrial fibrillation homozygous genotype (894 G/G) of the endothelial NO synthase (eNOS) gene was revealed in 62,2±7,2% (28 persons), heterozygous genotype (894 G/T) – in 33,3±7,0% (15 persons), homozygous genotype in a

A significant prevalence of homozygous genotype G/G as compared with the control group is established only in patients

52,10% 50,50%

Healthy relatives N=144

G/G 62 58,5±4,8 64 44,4±4,1 36 39,6±5,1 р>0,05 р<0,05 р>0,05 G/T 42 39,6±4,8 75 52,1±4,2 46 50,5±5,2 р>0,05 р>0,05 р>0,05 T/T 2 1,9±1,3 5 3,5±1,5 9 9,9±3,1 р>0,05 Р<0,05 р>0,05

> Genotype frequency of the eNOS 894 G/T polymorphism in patients with atrial fibrillation, their healthy relatives and persons of the control group.

**2.3 Polymorphism of the endothelial NO synthase (eNOS) gene in probands with atrial fibrillation, their healthy relatives and** 

**Absolute value**

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

% Absolute

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

P1-3<0,05

44,4% 39,6% 39,60%

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

rare allele (894 T/T) was genotyped in 4,4±3,1% (2 persons) (Table 8).

was genotyped in 4,4±3,1% (2 persons) (Table 8).

the difference is statistically reliable (р =0,021) (Table 8, Fig. 5).

control group (39,6%) is established; the difference is statistically reliable (р =0,039) (Table 7, Fig. 4).

genotype in a rare allele (894 T/T) was genotyped in 9,9±3,1% (9 persons) (Table 7).

**Control group N=91**

Control group N=91

value %

1,90%

3,50% 9,90%

**%**

**Absolute value**

Therefore, summarizing the abovementioned, homozygous genotype I/I of the gene ADRА2В may be regarded as one of the genetic predictors of primary atrial fibrillation onset. The relatives of the probands with primary atrial fibrillation and homozygous genotype I/I compose a high risk group for the appearance of this disorder. The conducted research of the gene ADRА2В polymorphism in patients with primary and secondary atrial fibrillation, can contribute to the decision of the etiological

In our work we investigated polymorphisms of the endothelial NO synthase (eNOS) gene in patients with atrial fibrillation , their healthy relatives and persons from the control group. According to the results of PCR in patients with atrial fibrillation, their healthy relatives and persons from the control group three sorts of NO synthase genotypes were revealed: G/G – homozygous, G/T –

Homozygous genotype (894 G/G) of the endothelial NO synthase (eNOS) gene in patients with atrial fibrillation was revealed in 58,5±4,8% (62 persons), heterozygous genotype (894 G/T) – in 39,6±4,8% (42 persons). Homozygous genotype in a rare

Among the probands' healthy relatives genotypes appeared to be spread as follows: homozygous genotype (894 G/G) –in 44,4±4,1% (64 persons), heterozygous genotype (894 G/T) – in 52,1±4,2% (75 persons), homozygous genotype in a rare allele (894 T/T) –in 3,5±1,5% (5 persons) (Table 7). As for the control group, homozygous genotype (894 G/G) of the gene of endothelial NO synthase was revealed in 39,6±5,1% (36 persons), heterozygous genotype (894 G/T) – in 50,5±5,2% (46 persons). Homozygous

A significant prevalence of homozygous genotype G/G in patients with atrial fibrillation (58,5%) as compared with the

**р1-2 р1-3 р2-3**

 Таблица 7

р1-2 р1-3 р2-3

**Table 8.** Genotype frequency of the eNOS 894 G/T polymorphism in patients with primary atrial fibrillation, their healthy relatives and persons of the control group. Genotypes fibrillation N= 45 Healthy relatives N=144 Control group N=91 р1-2 р1-3 р2-3 Абс. % Абс. % Абс. %

G/G 28 62,2±7,2 64 44,4±4,1 36 39,6±5,1 р>0,05 р<0,05 р>0,05 G/T 15 33,3±7,0 75 52,1±4,2 46 50,5±5,2 р>0,05 р>0,05 р>0,05 T/T 2 4,4±3,1 5 3,5±1,5 9 9,9±3,1 р>0,05 Р>0,05 р>0,05

Figure 5. Genotype frequency of the eNOS 894 G/T polymorphism in patients with primary atrial fibrillation, their healthy relatives

In patients with secondary atrial fibrillation homozygous genotype (894 G/G) of the endothelial NO synthase (eNOS) gene was revealed in 55,7±6,4% (34 persons), heterozygous genotype (894 G/T) – in 44,3±6,4% (27 persons), homozygous genotype in a **Figure 5.** Genotype frequency of the eNOS 894 G/T polymorphism in patients with primary atrial fibrillation, their healthy relatives and persons of the control group.

No significant differences were established between frequencies of genotypes of the endothelial NO synthase (eNOS) gene in patients with secondary atrial fibrillation, their healthy relatives and persons of the control group (Table 9, Fig. 6). Table 9 Genotype frequency of the eNOS 894 G/T polymorphism in patients with secondary atrial fibrillation, their healthy relatives and persons of the control group. Patients with In patients with secondary atrial fibrillation homozygous genotype (894 G/G) of the endo‐ thelial NO synthase (eNOS) gene was revealed in 55,7±6,4% (34 persons), heterozygous gen‐ otype (894 G/T) – in 44,3±6,4% (27 persons), homozygous genotype in a rare allele (894 T/T) was not genotyped (Table 9).

Genotypes fibrillation N= 61 N=144 N=91 р1-2 р1-3 р2-3 Absolute value % Absolute value % 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 No significant differences were established between frequencies of genotypes of the endo‐ thelial NO synthase (eNOS) gene in patients with secondary atrial fibrillation, their healthy relatives and persons of the control group (Table 9, Fig. 6).

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

Control group


**3. Conclusion**

group (39,6%) is shown.

development of heart rhythm disorders.

development of atrial fibrillation seems to be necessary.

care as well as on-time treatment of this type of arrhythmia.

ment of atrial fibrillation [45].

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.

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

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73

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.

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

The relatives of the probands with primary atrial fibrillation and homozygous genotype

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

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‐

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

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

G/G can be subsumed under the risk group for the development of this pathology.

migration of the Са from intracellular stores to the cytosol).

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

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

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

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.

**4. Acknowledgment**

**5. References** 

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.

**Table 9.** Genotype frequency of the eNOS 894 G/T polymorphism in patients with secondary atrial fibrillation, their healthy relatives and persons of the control group.

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 relatives and persons of the control group. **Figure 6.** Genotype frequency of the eNOS 894 G/T polymorphism in patients with secondary atrial fibrillation, their healthy relatives and persons of the control group.

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 fibrillation [42, 44]. 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 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].

kinases synthesis, all these factors contributing to the development of atrial fibrillation. The investigated genetic markers may be used in diagnosing of primary atrial fibrillation susceptibility. **3. Conclusion**  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 effector proteins (G-protein or receptor protein kinase), which cause changes in receptor activity autoregulation or associated with the activity cАМP processes of 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‐ rial fibrillation.

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

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
