**2. Results**

tion of potassium channels is increased. Thus, the data of Chinese researchers suggest that

H. Yang et al. [32] in their work also showed an increase in the amount of protein connexin 43 with atrial fibrillation, the highest in the left atrium. Christiansen J. et al. [33] found that mutation in gene 1q21.1, which leads to a decrease in connexin 40, promotes the develop‐ ment of abnormalities of the aortic arch with atrial fibrillation. Somatic mutations in the gene encoding gap - junction protein connexin 40 (GJA5), myocardial protein involved in the coordination of the electrical activity of the atria, can be a cause of idiopathic atrial fibril‐

"A significant part of patients have no obvious cause for the development of atrial fibrilla‐ tion and it is possible that 1/3 of these cases actually occurs due to mutations in GJA5 ", Mi‐ chael R. and H. Gollob wrote (University of Ottawa Heart Institute, Ontario, Canada). The findings, published in New England Journal of Medicine, are based on analysis of GJA5 in cardiac tissue and lymphocytes taken from 15 patients with idiopathic atrial fibrillation. Four out of all these patients had heterozygous mutations in GJA5. Three patients had muta‐ tions in heart tissue but not in lymphocytes, that indicates a somatic origin of the defects. The fourth patient's mutation was detected in both types of cells that suggest an embryonic mutation. Dr. H. Gollob believes that connexin 40 may become the object of search for new drugs to treat atrial fibrillation. The findings, according to the authors' opinion, suggest that the so-called idiopathic atrial fibrillation may have a genetic basis in the form of the defect,

By the present moment a large quantity of data is stored that activity of renin-angiotensinaldosterone system (RAAS) is of great importance for formation of this peculiar «cardio‐ myopathies of auricles». A key component of RAAS, significantly affecting its activity through the synthesis of angiotensin - II is a angiotensin-converting enzyme (ACE). ACE gene, located on chromosome 17q23, consists of 26 exons and 25 introns [35, 36]. ACE gene polymorphism concerns a fragment of intron 16 and it is connected with the insertion / dele‐ tion of 287 pairs of nucleotides and determines three genotypes - I / I, D / D and I / D. V.I. Tseluyko et al. showed that ACE levels in plasma are significantly higher in patients with genotype D / D than in genotype I / I. Heterozygotes have intermediate levels of ACE [37]. L.O. Minushkina, E.S. Gorshkova et al. (2010) studied association of genes β-adrenoceptors of types 1, 2, and 3 (ADRB1, ADRB2, ADRB3), connexin (CX40) and a voltage - locked potas‐ sium channel of type 2 (KCNH2) with the occurrence of atrial fibrillation in patients with hypertension. This study shows that for polymorphic marker Trp64Arg of gene ADRB3 Trp allele frequency was significantly higher and the frequency of the Arg allele was significant‐ ly lower in patients with atrial fibrillation. In patients with atrial fibrillation frequency of the

homozygous genotypes Arg / Arg appeared to be significantly less [38, 39].

According to the analysis conducted by J.D. Roberts, M.H. Michael, M.H. Gollob [10] at present a connection between atrial fibrillation and gene polymorphism of ion channels sub‐ units KCNQ1 [40], KCNA5 [41], KCNE2, KCNJ2, SCN5A, GJA5, NPPA is established. [10]. Several recent studies have focused on the association between the promoter polymor‐ phisms 786T/C of the endothelial nitric oxide synthase (eNOS) gene and susceptibility to at‐

certain variants of familial atrial fibrillation can be attributed to channelopathies.

lation in some cases [34].

62 Atrial Fibrillation - Mechanisms and Treatment

limited by the sick tissue.

#### **2.1. Clinical polymorphism of atrial fibrillation in probands and their relatives**

A total of 100 probands with atrial fibrillation and 150 of their relatives of the I st, II nd and III rd degree of relationship were examined. These families composed the study base for our research.

The probands were searched during the course of their in-patient and out-patient treatment in the Cardiological center of the Krasnoyarsk Regional clinical hospital № 20 named after I.S. Berzon. The patients' relatives were examined during doctors' home visits and subse‐ quent check-ups in the Cardiological center. We also studied 91 patients without electrocar‐ diographic manifestations of cardio-vascular diseases (control group).

The families of the probands with atrial fibrillation were divided into two groups according to the atrial fibrillation etiology:


The first group (families of the probands with primary atrial fibrillation) included 40 pro‐ bands (24 males and 16 females) and 79 of their relatives (23 males and 56 females), and the second one (families of the probands with secondary atrial fibrillation) included 60 pro‐ bands (28 males and 32 females) and 71 of their relatives (20 males and 51 females). Atrial fibrillation was revealed in 5 out of 79 relatives of the first group and in 1 out of 71 relatives of the second group. Differentiated clinical and electrocardiographic characteristics of the patients with primary atrial fibrillation are specified in Table 1.

Paroxysmal atrial fibrillation was revealed in 38 probands with primary atrial fibrillation (95,0±3,4%) and paroxysmal atrial flutter was revealed in 2 persons (5,0±3,4%). Among the sick relatives with primary atrial fibrillation (5 persons) paroxysmal atrial fibrillation was re‐ vealed in 5 persons (100%).


sclerosis – in 7 probands (11,7±5,8%). The II nd stage hypertension from the 1st to the 3rd degree was diagnosed in 12 probands (20,0±5,2%), the III rd stage hypertension from the 2nd to the 3rd degree was diagnosed in 4 persons (6,7±3,2%), gastroesophageal hernia – in 1 per‐ son, the 2nd degree nodular goiter with the appearance of euthyroidism as of the time of ex‐

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

In a small number of cases cardio-vascular pathologies were diagnosed in the probands with idiopathic atrial fibrillation: in 7 persons (17,5±6,0%) we diagnosed hypertension: 4 pa‐ tients (10,0±4,7%) had the Ist stage hypertension of the 1st degree, 3 patients (7,5±4,2%) had the IInd stage hypertension of the 1st- - 2nd degree, 4 probands (10,0±4,7%) had ischemic heart disease (II nd - III rd functional class effort angina). However atrial fibrillation seizures in pro‐ bands with primary atrial fibrillation were revealed long before the appearance of the first signs of ischemic heart disease and hypertension, therefore atrial fibrillation doesn't seem to be related to the revealed cardio-vascular diseases. As for the probands with secondary at‐ rial fibrillation, they showed temporal relation between the manifestations of the underlying

> **Probands with idiopathic atrial fibrillation (n=40)**

The Ist stage hypertension. 4 10,0±4,7 0 0 >0,05 The IInd stage hypertension. 3 7,5±4,2 12 20,0±5,2 >0,05 The IIIrd stage hypertension. 0 0 4 6,7±3,2 >0,05

Gastroesophageal hernia. 0 0 1 1,6±1,6 >0,05

**Table 3.** Cardio-vascular pathology in patients with idiopathic and secondary atrial fibrillation (& other diseases which

**%**

**Absolute value**

**Probands with the secondary atrial fibrillation**

**Absolute value**

0 0 6 10,0±3,9 >0,05

0 0 7 11,7±4,1 >0,05

4 10,0±4,7 29 48,3±6,5 <0,005

0 0 1 1,6±1,6 >0,05

**(n=60)** <sup>р</sup>

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

65

**%**

amination - in 1 person (1,6±1,6%).

**Disorders**

Ischemic heart disease combination (II nd - III rd functional class angina and the IIIrd stage hypertension).

Ischemic heart disease: postinfarction cardiosclerosis.

Ischemic heart disease: II nd - III rd functional class angina.

The 2nd degree nodular goiter with the appearance of euthyroidism as of the time of examination.

can cause atrial fibrillation)

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

disease and subsequent appearance of atrial fibrillation.

**Table 1.** Differentiated clinical and electrocardiographic characteristics of the patients with primary atrial fibrillation


**Table 2.** Differentiated clinical and electrocardiographic characteristics of the patients with secondary atrial fibrillation

According to Table 2, in the group of probands with secondary atrial fibrillation paroxysmal atrial fibrillation was diagnosed in 38 out of 60 patients (63,3±6,2%), paroxysmal atrial flutter – in 6 persons (10,0±3,9%). In total paroxysmal atrial fibrillation and atrial fibrillation - atrial flutter was observed in 73,3±5,7% of the probands with secondary atrial fibrillation. Chronic atrial fibrillation was revealed in 10 patients (16,6±4,8%), persistent atrial fibrillation – in 6 persons (10,0±3,9%). Due to the small number of persons in these groups, the probands with chronic and persistent atrial fibrillation were integrated into one group (chronic and persis‐ tent atrial fibrillation), which included 16 patients (26,6±5,7%).

Cardio-vascular pathology in the probands with idiopathic and secondary atrial fibrillation, as well as other diseases which have atrial fibrillation as a complication, are represented in Table 3. Namely, in 42 probands with secondary atrial fibrillation (70,0±5,9%) we revealed ischemic heart disease (effort angina of II-III functional class) in 29 persons, which made 48,3±7,1% of the total of probands of this group, II nd - III rd functional class effort angina to‐ gether with the III rd stage hypertension– in 6 probands (10,0±5,4%), postinfarction cardio‐ sclerosis – in 7 probands (11,7±5,8%). The II nd stage hypertension from the 1st to the 3rd degree was diagnosed in 12 probands (20,0±5,2%), the III rd stage hypertension from the 2nd to the 3rd degree was diagnosed in 4 persons (6,7±3,2%), gastroesophageal hernia – in 1 per‐ son, the 2nd degree nodular goiter with the appearance of euthyroidism as of the time of ex‐ amination - in 1 person (1,6±1,6%).

**Atrial fibrillation type**

64 Atrial Fibrillation - Mechanisms and Treatment

Paroxysmal atrial fibrillation and atrial fibrillation - atrial flutter summarily

**Atrial fibrillation type**

Paroxysmal atrial fibrillation and atrial fibrillation - atrial flutter summarily

tent atrial fibrillation), which included 16 patients (26,6±5,7%).

**Probands with primary atrial fibrillation (n=40)**

**Probands with secondary atrial fibrillation (n=60)**

**Absolute value**

Paroxysmal atrial fibrillation 38 63,3±6,2 1 100

Chronic atrial fibrillation 10 16,6±4,8 0 0 Persistent atrial fibrillation 6 10,0±3,9 0 0

Paroxysmal atrial fibrillation - atrial flutter 6 10,0±3,9 0 0

Chronic and persistent atrial fibrillation summarily 16 26,6±5,7 0 0

**Table 2.** Differentiated clinical and electrocardiographic characteristics of the patients with secondary atrial fibrillation

According to Table 2, in the group of probands with secondary atrial fibrillation paroxysmal atrial fibrillation was diagnosed in 38 out of 60 patients (63,3±6,2%), paroxysmal atrial flutter – in 6 persons (10,0±3,9%). In total paroxysmal atrial fibrillation and atrial fibrillation - atrial flutter was observed in 73,3±5,7% of the probands with secondary atrial fibrillation. Chronic atrial fibrillation was revealed in 10 patients (16,6±4,8%), persistent atrial fibrillation – in 6 persons (10,0±3,9%). Due to the small number of persons in these groups, the probands with chronic and persistent atrial fibrillation were integrated into one group (chronic and persis‐

Cardio-vascular pathology in the probands with idiopathic and secondary atrial fibrillation, as well as other diseases which have atrial fibrillation as a complication, are represented in Table 3. Namely, in 42 probands with secondary atrial fibrillation (70,0±5,9%) we revealed ischemic heart disease (effort angina of II-III functional class) in 29 persons, which made 48,3±7,1% of the total of probands of this group, II nd - III rd functional class effort angina to‐ gether with the III rd stage hypertension– in 6 probands (10,0±5,4%), postinfarction cardio‐

**%**

**%**

40 100 0 0

44 73,3±5,7 0 0

**Absolute value**

Paroxysmal atrial fibrillation 38 95,0±3,4 5 100

Paroxysmal atrial fibrillation - atrial flutter 2 5,0±3,4 0 0

**Table 1.** Differentiated clinical and electrocardiographic characteristics of the patients with primary atrial fibrillation

**Probands'sick relatives (n=5)**

**Probands'sick relatives (n=1)**

**Absolute value**

**%**

**%**

**Absolute value**

> In a small number of cases cardio-vascular pathologies were diagnosed in the probands with idiopathic atrial fibrillation: in 7 persons (17,5±6,0%) we diagnosed hypertension: 4 pa‐ tients (10,0±4,7%) had the Ist stage hypertension of the 1st degree, 3 patients (7,5±4,2%) had the IInd stage hypertension of the 1st- - 2nd degree, 4 probands (10,0±4,7%) had ischemic heart disease (II nd - III rd functional class effort angina). However atrial fibrillation seizures in pro‐ bands with primary atrial fibrillation were revealed long before the appearance of the first signs of ischemic heart disease and hypertension, therefore atrial fibrillation doesn't seem to be related to the revealed cardio-vascular diseases. As for the probands with secondary at‐ rial fibrillation, they showed temporal relation between the manifestations of the underlying disease and subsequent appearance of atrial fibrillation.


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

**Table 3.** Cardio-vascular pathology in patients with idiopathic and secondary atrial fibrillation (& other diseases which can cause atrial fibrillation)

Therefore, summarizing the abovementioned, we come to the following conclusion.

In the first group (primary atrial fibrillation) paroxysmal atrial fibrillation was dominant (re‐ vealed in all the patients). In probands with secondary atrial fibrillation a significant preva‐ lence of chronic/persistent atrial fibrillation was diagnosed (in 16 out of 60 persons (26,6±5,7%).

A significant prevalence of homozygous genotype I/I in patients with AF (40,6%) compared

50,90% 50,70%

DD ID II 1 Patients with atrial fibrillation (n=106) 2 Healthy relatives (n=144) 3 Control group (n=91)

Figure 1. Frequency of the gene ADRA2B genotypes in probands with atrial fibrillation, their healthy relatives and persons of the

**Figure 1.** Frequency of the gene ADRA2B genotypes in probands with atrial fibrillation, their healthy relatives and per‐

In patients with primary atrial fibrillation frequency of the homozygous genotypes (D/D) made 6,7±3,7% (3 persons), frequency of the heterozygous genotype (I/D) made 48,9±7,5% (22 persons), frequency of the homozygous genotype in a rare allele (I/I) made 44,4±7,4% (20 persons) (Table 5). A significant prevalence of homozygous genotype I/I as compared with the control group (25,3%) is established only in patients with primary atrial fibrillation

Frequency of the gene ADRA2B genotypes in patients with primary atrial fibrillation, their healthy relatives and persons of the control group.

group (25,3%) is established only in patients with primary atrial fibrillation (44,4%) (р = 0,039) (Table 5, Fig. 2).

Healthy relatives N=144

**Healthy relatives N=144**

**%**

In patients with primary atrial fibrillation frequency of the homozygous genotypes (D/D) made 6,7±3,7% (3 persons), frequency of the heterozygous genotype (I/D) made 48,9±7,5% (22 persons), frequency of the homozygous genotype in a rare allele (I/I) made 44,4±7,4% (20 persons) (Table 5). A significant prevalence of homozygous genotype I/I as compared with the control

> % Absolute value

D/D 3 6,7±3,7 17 11,8±2,7 10 11±3,3 р>0,05 р>0,05 р>0,05 I/D 22 48,9±7,5 73 50,7±4,2 58 63,7±5,0 р>0,05 р>0,05 р>0,05 I/I 20 44,4±7,4 54 37,5±4,0 23 25,3±4,6 р>0,05 р<0,05 р>0,05

D/D 3 6,7±3,7 17 11,8±2,7 10 11±3,3 р>0,05 р>0,05 р>0,05

I/D 22 48,9±7,5 73 50,7±4,2 58 63,7±5,0 р>0,05 р>0,05 р>0,05

I/I 20 44,4±7,4 54 37,5±4,0 23 25,3±4,6 р>0,05 р<0,05 р>0,05

**Table 5.** Frequency of the gene ADRA2B genotypes in patients with primary atrial fibrillation, their healthy relatives

Control group N=91

%

**Control group N=91**

**%**

**Absolute value**

In persons of the control group (D/D) frequency of the homozygous genotype made 11,0±3,3% (10 persons), frequency of the heterozygous genotype (genotype I/D) made 63,7±5,0% (58 persons), frequency of the homozygous genotype in a rare allele (I/I)

A significant prevalence of homozygous genotype I/I in patients with AF (40,6%) compared with the control group

63,70%

40,60% 37,50%

P1-3<0,05

25,30%

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67

Table 5.

р1-2 р1-3 р2-3

**р1-2 р1-3 р2-3**

I/D 54 50,9±4,9 73 50,7±4,2 58 63,7±5,0 р>0,05 р>0,05 р>0,05 I/I 43 40,6±4,8 54 37,5±4,0 23 25,3±4,6 р>0,05 р<0,05 р>0,05

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

with the control group (25,3%) (р = 0,034) was established (Table 4, Fig.1).

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

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

% Absolute value

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

**Absolute value**

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

**%**

made 25,3±4,6% (23 persons) (Table 4).

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

control group.

sons of the control group.

Genotypes

**Genotypes**

(25,3%) (р = 0,034) was established (Table 4, Fig.1).

8,50% 11,80% 11,0%

Patients with primary atrial fibrillation N= 45

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

Absolute value

**Absolute value**

and persons of the control group.

(44,4%) (р = 0,039) (Table 5, Fig. 2).

In the probands with primary atrial fibrillation paroxysmal atrial fibrillation had been re‐ vealed long before any cardio-vascular diseases manifestations appeared.

#### **2.2. Polymorphism of the gene ADRA2B in probands with atrial fibrillation, their healthy relatives and persons of the control group**

In our work we investigated polymorphisms of the gene ADRА2В in patients with atrial fi‐ brillation, their healthy relatives and persons from the control group. According to the re‐ sults of PCR three sorts of genotypes ADRA2B in patients with AF, their healthy relatives and persons from the control group are revealed: I / I - homozygous by the insertion, I / D heterozygous, D / D - homozygous by the deletion. In patients with atrial fibrillation fre‐ quency of the homozygous genotype (D/D) made 8,5±2,7% (9 persons), whereas frequency of the heterozygous genotype (genotype I/D) made 50,9±4,9% (54 persons), frequency of the homozygous genotype in a rare allele (I/I) made 40,6±4,8% (43 persons) (Table 4).

Frequency of the homozygous genotypes among the probands' healthy relatives appeared to be spread as follows: homozygous genotype in a frequent allele (D/D) made 11,8±2,7% (17 persons), heterozygous genotype (I/D) – 50,7±4,2% (73 persons), homozygous genotype in a rare allele (I/I) – 37,5±4,0% (54 persons) (Table 4).


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

**Table 4.** Frequency of the gene ADRA2B genotypes in probands with atrial fibrillation, their healthy relatives and persons of the control group.

In persons of the control group (D/D) frequency of the homozygous genotype made 11,0±3,3% (10 persons), frequency of the heterozygous genotype (genotype I/D) made 63,7±5,0% (58 persons), frequency of the homozygous genotype in a rare allele (I/I) made 25,3±4,6% (23 persons) (Table 4).

A significant prevalence of homozygous genotype I/I in patients with AF (40,6%) compared with the control group (25,3%) (р = 0,034) was established (Table 4, Fig.1). In persons of the control group (D/D) frequency of the homozygous genotype made 11,0±3,3% (10 persons), frequency of the heterozygous genotype (genotype I/D) made 63,7±5,0% (58 persons), frequency of the homozygous genotype in a rare allele (I/I) made 25,3±4,6% (23 persons) (Table 4). A significant prevalence of homozygous genotype I/I in patients with AF (40,6%) compared with the control group

I/I 43 40,6±4,8 54 37,5±4,0 23 25,3±4,6 р>0,05 р<0,05 р>0,05

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

(25,3%) (р = 0,034) was established (Table 4, Fig.1).

Absolute

Therefore, summarizing the abovementioned, we come to the following conclusion.

vealed long before any cardio-vascular diseases manifestations appeared.

**relatives and persons of the control group**

66 Atrial Fibrillation - Mechanisms and Treatment

rare allele (I/I) – 37,5±4,0% (54 persons) (Table 4).

**%**

**Patients with atrial fibrillation N= 106**

**Absolute value**

persons of the control group.

25,3±4,6% (23 persons) (Table 4).

(26,6±5,7%).

**Genotypes**

In the first group (primary atrial fibrillation) paroxysmal atrial fibrillation was dominant (re‐ vealed in all the patients). In probands with secondary atrial fibrillation a significant preva‐ lence of chronic/persistent atrial fibrillation was diagnosed (in 16 out of 60 persons

In the probands with primary atrial fibrillation paroxysmal atrial fibrillation had been re‐

**2.2. Polymorphism of the gene ADRA2B in probands with atrial fibrillation, their healthy**

In our work we investigated polymorphisms of the gene ADRА2В in patients with atrial fi‐ brillation, their healthy relatives and persons from the control group. According to the re‐ sults of PCR three sorts of genotypes ADRA2B in patients with AF, their healthy relatives and persons from the control group are revealed: I / I - homozygous by the insertion, I / D heterozygous, D / D - homozygous by the deletion. In patients with atrial fibrillation fre‐ quency of the homozygous genotype (D/D) made 8,5±2,7% (9 persons), whereas frequency of the heterozygous genotype (genotype I/D) made 50,9±4,9% (54 persons), frequency of the

Frequency of the homozygous genotypes among the probands' healthy relatives appeared to be spread as follows: homozygous genotype in a frequent allele (D/D) made 11,8±2,7% (17 persons), heterozygous genotype (I/D) – 50,7±4,2% (73 persons), homozygous genotype in a

> **Control group N=91**

> > **%**

**Absolute value**

D/D 9 8,5±2,7 17 11,8±2,7 10 11±3,3 р>0,05 р>0,05 р>0,05 I/D 54 50,9±4,9 73 50,7±4,2 58 63,7±5,0 р>0,05 р>0,05 р>0,05 I/I 43 40,6±4,8 54 37,5±4,0 23 25,3±4,6 р>0,05 р<0,05 р>0,05

**Table 4.** Frequency of the gene ADRA2B genotypes in probands with atrial fibrillation, their healthy relatives and

In persons of the control group (D/D) frequency of the homozygous genotype made 11,0±3,3% (10 persons), frequency of the heterozygous genotype (genotype I/D) made 63,7±5,0% (58 persons), frequency of the homozygous genotype in a rare allele (I/I) made

**р1-2 р1-3 р2-3**

homozygous genotype in a rare allele (I/I) made 40,6±4,8% (43 persons) (Table 4).

**Healthy relatives N=144**

**%**

**Absolute value**

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

 *Note: Differences in the investigated parameters were calculated using the χ2 criterion.*  Figure 1. Frequency of the gene ADRA2B genotypes in probands with atrial fibrillation, their healthy relatives and persons of the control group. **Figure 1.** Frequency of the gene ADRA2B genotypes in probands with atrial fibrillation, their healthy relatives and per‐ sons of the control group.

In patients with primary atrial fibrillation frequency of the homozygous genotypes (D/D) made 6,7±3,7% (3 persons), frequency of the heterozygous genotype (I/D) made 48,9±7,5% (22 persons), frequency of the homozygous genotype in a rare allele (I/I) made 44,4±7,4% (20 persons) (Table 5). A significant prevalence of homozygous genotype I/I as compared with the control group (25,3%) is established only in patients with primary atrial fibrillation (44,4%) (р = 0,039) (Table 5, Fig. 2). Table 5. Frequency of the gene ADRA2B genotypes in patients with primary atrial fibrillation, their healthy relatives and persons of the control group. Genotypes Patients with primary atrial fibrillation N= 45 Healthy relatives N=144 Control group N=91 р1-2 р1-3 р2-3 In patients with primary atrial fibrillation frequency of the homozygous genotypes (D/D) made 6,7±3,7% (3 persons), frequency of the heterozygous genotype (I/D) made 48,9±7,5% (22 persons), frequency of the homozygous genotype in a rare allele (I/I) made 44,4±7,4% (20 persons) (Table 5). A significant prevalence of homozygous genotype I/I as compared with the control group (25,3%) is established only in patients with primary atrial fibrillation (44,4%) (р = 0,039) (Table 5, Fig. 2).

% Absolute

%


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

% Absolute

**Table 5.** Frequency of the gene ADRA2B genotypes in patients with primary atrial fibrillation, their healthy relatives and persons of the control group.

Absolute value

0%

the gene ADRА2В polymorphism in patients with primary and secondary atrial fibrillation,

D/D 6 9,8±3,8 17 11,8±2,7 10 11±3,3 р>0,05 р>0,05 р>0,05 I/D 32 52,5±6,4 73 50,7±4,2 58 63,7±5.0 р>0,05 р>0,05 р>0,05 I/I 23 37,7±6,2 54 37,5±4,0 23 25,3±4,6 р>0,05 р>0,05 р>0,05

Absol ute value

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

48,90% 50,70%

**DD ID II** 1 Patients with primary atrial fibrillation (n=45) 2 Healthy relatives (n=144) 3 Control group (n=91)

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

Figure 2. Frequency of the gene ADRA2B genotypes in patients with primary atrial fibrillation, their healthy relatives and persons of

Frequency of the gene ADRA2B genotypes in patients with secondary atrial fibrillation, their healthy relatives and persons of the control group.

Among patients with primary atrial fibrillation frequency of the genotypes appeared to be spread as follows: homozygous genotype (D/D) made 9,8±3,8% (6 persons), heterozygous genotype (I/D) – 52,5±6,4% (32 persons), homozygous genotype in a rare

No significant differences were established between frequencies of I/D genotypes of the gene ADRA2B in patients with

Control group N=91

63,70%

%

63,70%

44,40%

37,50%

P1-3<0,05

р1-2 р1-3 р2-3

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

25,30%

37,70% 37,50%

P1-3>0,05

25,30%

Table 6.

69

can contribute to the decision of the etiological issue of hereditary atrial fibrillation.

52,50% 50,70%

DD ID II

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

Figure 3. Frequency of the gene ADRA2B genotypes in patients with secondary atrial fibrillation, their healthy relatives and persons

**Figure 3.** Frequency of the gene ADRA2B genotypes in patients with secondary atrial fibrillation, their healthy rela‐

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 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‐

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

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‐

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

secondary atrial fibrillation, their healthy relatives and persons of the control group. (Table 6, Fig.3).

Healthy relatives N=144

value %

% 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.*

homozygous, G/T – heterozygous, T/T – homozygous.

typed in 1,9±1,3% (2 persons) (Table 7).

genotyped in 9,9±3,1% (9 persons) (Table 7).

cally reliable (р =0,039) (Table 7, Fig. 4).

9,80% 11,80% 11,0%

6,70% 11,80% 11,0%

allele (genotype I/I) – 37,7±6,2% (23 persons) (Table 6).

Patients with secondary atrial fibrillation N= 61

Absolute value

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

the control group.

Genotypes

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

of the control group.

**the control group**

tives and persons of the control group.

Figure 2. Frequency of the gene ADRA2B genotypes in patients with primary atrial fibrillation, their healthy relatives and persons of the control group. **Figure 2.** Frequency of the gene ADRA2B genotypes in patients with primary atrial fibrillation, their healthy relatives and persons of the control group.

Among patients with primary atrial fibrillation frequency of the genotypes appeared to be spread as follows: homozygous

genotype (D/D) made 9,8±3,8% (6 persons), heterozygous genotype (I/D) – 52,5±6,4% (32 persons), homozygous genotype in a rare allele (genotype I/I) – 37,7±6,2% (23 persons) (Table 6). No significant differences were established between frequencies of I/D genotypes of the gene ADRA2B in patients with secondary atrial fibrillation, their healthy relatives and persons of the control group. (Table 6, Fig.3). Table 6. Frequency of the gene ADRA2B genotypes in patients with secondary atrial fibrillation, their healthy relatives and persons of the control group. Among patients with primary atrial fibrillation frequency of the genotypes appeared to be spread as follows: homozygous genotype (D/D) made 9,8±3,8% (6 persons), heterozygous genotype (I/D) – 52,5±6,4% (32 persons), homozygous genotype in a rare allele (genotype I/I) – 37,7±6,2% (23 persons) (Table 6).

Genotypes Patients with secondary atrial fibrillation N= 61 Healthy relatives N=144 Control group N=91 р1-2 р1-3 р2-3 No significant differences were established between frequencies of I/D genotypes of the gene ADRA2B in patients with secondary atrial fibrillation, their healthy relatives and per‐ sons of the control group. (Table 6, Fig.3).

> Absol ute

%


10% Note: Differences in the investigated parameters were calculated using the χ2 criterion.

% Absolute

value %

DD ID II 1 Patients with secondary atrial fibrillation (n=61) 2 Healthy relatives (n=144) 3 Control group (n=91) **Table 6.** Frequency of the gene ADRA2B genotypes in patients with secondary atrial fibrillation, their healthy relatives and persons of the control group.

*Note: Differences in the investigated parameters were calculated using the χ2 criterion.* Figure 3. Frequency of the gene ADRA2B genotypes in patients with secondary atrial fibrillation, their healthy relatives and persons of the control group. 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 on‐ set. 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

Control group N=91

the gene ADRА2В polymorphism in patients with primary and secondary atrial fibrillation, can contribute to the decision of the etiological issue of hereditary atrial fibrillation. D/D 6 9,8±3,8 17 11,8±2,7 10 11±3,3 р>0,05 р>0,05 р>0,05 I/D 32 52,5±6,4 73 50,7±4,2 58 63,7±5.0 р>0,05 р>0,05 р>0,05 I/I 23 37,7±6,2 54 37,5±4,0 23 25,3±4,6 р>0,05 р>0,05 р>0,05 *Note: Differences in the investigated parameters were calculated using the χ2 criterion.* 

48,90% 50,70%

**DD ID II** 1 Patients with primary atrial fibrillation (n=45) 2 Healthy relatives (n=144) 3 Control group (n=91)

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

Figure 2. Frequency of the gene ADRA2B genotypes in patients with primary atrial fibrillation, their healthy relatives and persons of

Frequency of the gene ADRA2B genotypes in patients with secondary atrial fibrillation, their healthy relatives and persons of the control group.

secondary atrial fibrillation, their healthy relatives and persons of the control group. (Table 6, Fig.3).

Healthy relatives N=144

Among patients with primary atrial fibrillation frequency of the genotypes appeared to be spread as follows: homozygous genotype (D/D) made 9,8±3,8% (6 persons), heterozygous genotype (I/D) – 52,5±6,4% (32 persons), homozygous genotype in a rare

No significant differences were established between frequencies of I/D genotypes of the gene ADRA2B in patients with

63,70%

44,40%

37,50%

P1-3<0,05

25,30%

Table 6.

6,70% 11,80% 11,0%

allele (genotype I/I) – 37,7±6,2% (23 persons) (Table 6).

Patients with secondary atrial fibrillation

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

the control group.

6,70% 11,80% 11,0%

allele (genotype I/I) – 37,7±6,2% (23 persons) (Table 6).

Patients with secondary atrial fibrillation N= 61

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

sons of the control group. (Table 6, Fig.3).

– 37,7±6,2% (23 persons) (Table 6).

Absolute value

**Absolute value**

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

the control group.

and persons of the control group.

68 Atrial Fibrillation - Mechanisms and Treatment

Genotypes

**Genotypes**

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

and persons of the control group.

of the control group.

48,90% 50,70%

**DD ID II** 1 Patients with primary atrial fibrillation (n=45) 2 Healthy relatives (n=144) 3 Control group (n=91)

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

Figure 2. Frequency of the gene ADRA2B genotypes in patients with primary atrial fibrillation, their healthy relatives and persons of

**Figure 2.** Frequency of the gene ADRA2B genotypes in patients with primary atrial fibrillation, their healthy relatives

Among patients with primary atrial fibrillation frequency of the genotypes appeared to be spread as follows: homozygous genotype (D/D) made 9,8±3,8% (6 persons), heterozygous genotype (I/D) – 52,5±6,4% (32 persons), homozygous genotype in a rare allele (genotype I/I)

> Frequency of the gene ADRA2B genotypes in patients with secondary atrial fibrillation, their healthy relatives and persons of the control group.

No significant differences were established between frequencies of I/D genotypes of the gene ADRA2B in patients with secondary atrial fibrillation, their healthy relatives and per‐

> Absol ute value

D/D 6 9,8±3,8 17 11,8±2,7 10 11±3,3 р>0,05 р>0,05 р>0,05 I/D 32 52,5±6,4 73 50,7±4,2 58 63,7±5.0 р>0,05 р>0,05 р>0,05 I/I 23 37,7±6,2 54 37,5±4,0 23 25,3±4,6 р>0,05 р>0,05 р>0,05

52,50% 50,70%

D/D 6 9,8±3,8 17 11,8±2,7 10 11±3,3 р>0,05 р>0,05 р>0,05 I/D 32 52,5±6,4 73 50,7±4,2 58 63,7±5.0 р>0,05 р>0,05 р>0,05 I/I 23 37,7±6,2 54 37,5±4,0 23 25,3±4,6 р>0,05 р>0,05 р>0,05

**%**

DD ID II

**Table 6.** Frequency of the gene ADRA2B genotypes in patients with secondary atrial fibrillation, their healthy relatives

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

Figure 3. Frequency of the gene ADRA2B genotypes in patients with secondary atrial fibrillation, their healthy relatives and persons

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 on‐ set. 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

secondary atrial fibrillation, their healthy relatives and persons of the control group. (Table 6, Fig.3).

Healthy relatives N=144

value %

**Healthy relatives N=144**

% Absolute

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

**Absolute value**

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

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

9,80% 11,80% 11,0%

**%**

Among patients with primary atrial fibrillation frequency of the genotypes appeared to be spread as follows: homozygous genotype (D/D) made 9,8±3,8% (6 persons), heterozygous genotype (I/D) – 52,5±6,4% (32 persons), homozygous genotype in a rare

No significant differences were established between frequencies of I/D genotypes of the gene ADRA2B in patients with

Control group N=91

63,70%

**Absolute value**

%

**Control group N=91**

**%**

63,70%

44,40%

37,50%

P1-3<0,05

р1-2 р1-3 р2-3

25,30%

**р1-2 р1-3 р2-3**

37,70% 37,50%

P1-3>0,05

25,30%

Table 6.

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

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

Figure 3. Frequency of the gene ADRA2B genotypes in patients with secondary atrial fibrillation, their healthy relatives and persons of the control group. **Figure 3.** Frequency of the gene ADRA2B genotypes in patients with secondary atrial fibrillation, their healthy rela‐ tives and persons of the control group.
