**7. G-protein β3 subunit C825T gene polymorphism**

G-protein β3 subunit C825T gene polymorphism plays an important role in the change of electrophysiological properties of human atrium. This polymorphism occurs in 10th exon of gene, which encodes the G-protein β3 subunit. It has been determined by Siffert et al. that this polymorphism is a genetic risk factor in the development of hypertension. Increased human atrial internal rectifier regulatory potentials have been associated with the TT genotype of G-protein β3 subunit C825T gene polymorphism. There is also a significant relationship between the TT genotype of the G-protein β3 subunit C825T gene polymorphism and the increased internal rectifier flow and reduced acetylcholine stimulating potassium flux in the human atrium. In the European white population, 825 T allele of G-protein β3 subunit C825T gene polymorphism was found to be significantly associated with various cardiovascular disorders such as increased obesity, hypertension, left ventricular hypertrophy and coronary artery disease. In a study performed by Schreieck et al., heterozygote T and homozygote T allele carriage were found to be low risk factors for AF development. G-protein β3 subunit the TT and CT genotypes of the C825T gene polymorphism play an important role in atrial cellular electrophysiological changes. In a study conducted by Dobrev et al., it was determined that TT genotype of this polymorphism correlates with the downregulation of acetylcholine mRNA transcripts in human atrial myocytes. Although there is no relationship between G-protein β3 subunit C825T gene polymorphism and any arrhythmia, in some studies this polymorphism has been associated with the risk of developing AF. In conclusion, gene polymorphisms encoding ion channels are very important in AF pathogenesis. Identification of these polymorphisms will elucidate the multigenic mechanism of AF predisposition [16]. It is presented primer sequences that used to determine G-protein β3 subunit C825T gene polymorphism in **Table 7**.

are more important in the development of early onset AF. The relationship between these gene polymorphisms and the risk of developing AF has been explored in different populations. From these populations, in one Chinese and European origin considerable differences have been found in terms of these polymorphisms. rs2200733 on the 4q25 chromosome and rs106261 gene polymorphisms on the 16q22 chromosome have been observed quite often in the Chinese population in particular. However, the relationship between the rs7193343 gene polymorphism on the 16q22 chromosome and the risk of developing AF was not significant in the Chinese Han population. In a study conducted by Ellinor et al. with the European population, KCNN3 single nucleotide gene polymorphism, which is associated with AF in the new genetic locus, has been discovered in the potassium medium/small conductance calciumactivating channel. The KCNN3 gene encodes voltage-independent calcium and activated potassium channels. The KCNN3 rs13376333 gene polymorphism is located between the first and second exons of the KCNN3 gene. There are three subtypes of potassium channels as SK1, SK2 and SK3. Atrial myocytes are formed by the subunits of these channels to form heteromultimeric complexes. The expression of SK3 channels is similar to the expressions of SK1 and SK2 channels. There are studies showing that the relationship between these SK channels and AF is significant. However, more studies are needed to determine the role of SK3 channels in AF development. Studies were also conducted in the Asian population to investigate AF associations with KCNN3 gene polymorphisms, which are the ionic channel gene identified in AF GWAS. However, a large number of replication studies are needed to determine this relationship. In a study conducted by Chang et al., KCNN3 rs13376333 gene polymorphism in the Taiwanese population was found to be an important risk factor for the development of AF. Also Ellinor et al. showed that there is a significant association between AF and KCNN3 rs13376333 gene polymorphism. In a study conducted with Chinese Han population, KCNN3 rs13376333 gene polymorphism has not been identified as a genetic risk factor in the development of AF. In Taiwan and China populations, the T allele of KCNN3

Gene Polymorphisms Associated with Atrial Fibrillation http://dx.doi.org/10.5772/intechopen.76920 13

rs13376333 gene polymorphism was observed at a significantly lower frequency [17].

Voltage-gated sodium channels play an important role in impulse generation and conduction during the rising phase of action potential in excitable cells. There are sodium channel isoforms in the heart. These channels include voltage-gated sodium 1.1, voltage-gated sodium

duction. The Nav1.5 channel plays a very important role in cardiac impulse spread. As a result of the activation of sodium channels, the cardiac action potential is rapidly increasing. Each sodium channel consists of an α subunit and modulating β subunits. The α subunit of the NaV1.5 channel is encoded by the SCN5A gene. Each of the Nav1.5 α subunit consists of 4 homologous domains (DI-DIV) with 6 transmembrane alpha helices (S1-S6). The S1-S4 domains are repeatable and these domains constitute the voltage sensing areas of the channel. The functional pore and selectivity filter of the sodium channel consists of S5, S6 and S5-S6 loops. More than 300 mutations have been identified in the SCN5A gene. SCN5A mutations determined to be associated with Brugada Syndrome (BrS) lead to variable reductions in the sodium flow inward with channel transit changes. These channel passing changes delayed

1.5), voltage-gated sodium 1.6 and voltage-gated sodium

1.5 encoded by SCN5A is responsible for the regulation of cardiac con-

**8.2. SCN10A gene polymorphism**

1.3, voltage-gated sodium 1.5 (Nav

1.8 channels. The Nav


PCR, polymerase chain reaction.

**Table 7.** Sequence of primers for G-protein β3 subunit C825T gene polymorphism.
