**11. Gene polymorphisms on chromosome 4q25**

at the onset or maintenance of AF. The arrhythmia matrix is formed by the interaction of proteins encoded by KCNE1 with other proteins. Therefore, the KCNE1 gene plays a very important role in regulating cardiac rhythm. Studies involving subgroup analyzes also found that the risk of developing AF in white populations with risk alleles was higher than in the Chinese population. The pathogenesis of AF is unknown. However, as a result of mutations in the genes encoding the ion channel, AF can develop due to a decrease in IKs. Environmental factors and genetic factors play a role in the pathogenesis of AF. It has been determined that different polymorphisms in genes encoding ion channels other than the KCNE1 G38S gene polymorphism may also be important risk factors for AF development [24, 25]. It is presented primer sequences that used to

A polygenic process involving transcription factors, cardiac ion channels, myocardial and cytoskeletal proteins plays an important role in AF pathogenesis. Based on the entire genome sequence, GWAS has shown that three low-frequency coding variants are effective in the development of AF. The myosin sarcomeric genes MYH6 and MYL4, the cytoskeletal gene PLEC, are these variants. MYH6, MYL4 and PLEC genes also encode cardiomyocyte structural components such as MYZAP. Ribosome activity can be specifically regulated in the cell via changes in the ribozyme protein composition. The eukaryotic ribosome consists of 4 different ribosomal RNAs and about 80 ribosomal proteins. This ribosome plays an important role in translating the messenger mRNA into a protein. Ribosomal proteins or genes encoding ribosome biogenesis factors may result in mutations leading to ribosomopathy, a hereditary disease. It is known that RPL3L-containing ribosomes may cause translational activity changes. Among RPL3L missense mutations, a negative regulator of muscle growth, p.Ala75Val and p.Gly12Arg mutations are important. Apart from these mutations, the RPL3L c.1167+1G>A mutation is involved in the impairment of the interaction of RPL3L with endoplasmic reticulum. As a result of these mutations, the risk of developing AF is increasing. Human Myozap mRNA is expressed primarily in the heart. Myozap regulates serum response factor signaling in the nucleus. This is why it plays an important role in cardiac signal transduction. Mutations in intercalated disk genes result in cardiomyopathies and sudden cardiac deaths that are a significant risk for AF. AF variants are defined in the genes coding for components of intercalated discs and in the vicinity of these genes. Seeger et al. found the MYZAP gene in the components of intercalated discs. Intercalated discs are a cell-cell contact structure that provides mechanical, electrical and chemical communication between cardiomyocytes. The risk of AF is also increasing as a result of MYZAP p.Gln254Pro gene polymorphism. In a previous study, there was a significant relationship between four lowfrequency coding variants in the RPL3L and MYZAP genes and the risk of developing AF. The missense variant in MYZAP was identified as a genetic risk factor in the development of AF [26].

**10. Gene polymorphisms and C-reactive protein levels related to** 

Several studies have been carried out to investigate the relationship between inflammation and AF. These studies have led to the conclusion that inflammation may cause AF or play an important

**inflammation**

16 Cardiac Arrhythmias

determine polymorphisms in the genes coding ion channels in **Table 8**.

**9. RPL3L and MYZAP gene polymorphisms**

There are four unique nucleotide polymorphisms on the 4q25 chromosomal region, rs2200733, rs2220427, rs2634073 and rs10033464, and in studies conducted in European and Chinese populations, a significant relationship was found between these polymorphisms and the risk of developing AF. There are no known biological roles of these single nucleotide polymorphisms. These polymorphisms near to the homedomain transcription factor 2 (PITX2) gene and potentially alter the function of this factor. PITX2 is involved in the cardiac pathogenesis of ischemic and pulmonary venous access pathways. rs2200733 and rs13143308 that among the polymorphisms found on the 4q25 chromosome have also been identified as genetic risk factors for AF development. There are also several epidemiological cohorts recently showing a significant association between rs2200733, rs10033464 single nucleotide polymorphisms located in the 4q25 chromosome and AF development. In a recent study, rs2200733 polymorphism was found to be a genetic risk factor for AF development, proliferation and recurrence [28].
