PITX2 and NEURL1 SNP polymorphisms in Hungarian atrial fibrillation patients determined by quantitative real-time PCR and melting curve analysis

• Published in: Journal of biotechnology Vol. 299; pp. 44 - 49
• Main Authors: Szirák, Krisztina, Soltész, Beáta, Hajas, Orsolya, Urbancsek, Réka, Nagy-Baló, Edina, Penyige, András, Csanádi, Zoltán, Nagy, Bálint
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.06.2019
• Subjects: Adaptor Proteins, Signal Transducing; Adult; Aged; Atrial fibrillation; Atrial Fibrillation - genetics; Atrial Fibrillation - metabolism; beta Catenin - metabolism; Calcium-Binding Proteins; Case-Control Studies; Female; Gene Frequency; Genetic Predisposition to Disease; Homeobox Protein PITX2; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humans; Hungary; Intercellular Signaling Peptides and Proteins - metabolism; Jagged-1 Protein - metabolism; Male; Middle Aged; NEURL1; PITX2; Polymorphism, Single Nucleotide; Protein Interaction Maps; Real-Time Polymerase Chain Reaction; rs2595104; rs6584555; Single nucleotide polymorphism; Transcription Factors - genetics; Transcription Factors - metabolism; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; White People - genetics; Hungary; rs2595104; AF; Atrial fibrillation; rs6584555; NEURL1; Single nucleotide polymorphism; PITX2
• ISSN: 0168-1656; 1873-4863
• DOI: 10.1016/j.jbiotec.2019.04.022

•The allele and genotype frequencies of the SNP in the enhancer region of PITX2 (rs 2595104) and the SNP in the NEURL1 gene (rs 6584555) were determined in a healthy population and in patients having atrial fibrillation.•The linkage disequilibrium was calculated between the two loci.•We found indirect interactions between PITX2 and NEURL1 gene products via either beta-cathenin encoded by CTNNB1 and JAG1 or beta-cathenin and DLL4 proteins. Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting 1–2% of the general population. Some common variants located in or next to PITX2 and NEURL1 genes are proved to play role in the occurrence of AF. The aim of our study was to investigate whether rs2595104 in the 4q25 chromosome region and rs6584555 SNP in the NEURL1 gene on chromosome 10 is associated with AF in a Caucasian population. We genotyped DNA samples of 76 AF patients and 77 healthy controls using quantitative real-time PCR followed by melting curve analysis. The minor A allele frequency of rs2595104 in PITX2 was 0.38 and 0.44 in the control group and in AF patients, respectively. There was no significant difference in allele and genotype distribution between the two groups (p = 0.52). The allele frequency based log additive odds ratio is 1.22 (C.I. = 0.76–1.94; p = 0.42). The frequency of minor rs6584555 C allele in NEURL1 was 0.22 in the control group and 0.23 in AF patients. Again there were no significant differences in allele and genotype frequencies between AF patients and controls (p = 0.92). The log additive odds ratio is 1,15 (C.I. = 0.66–2.01; p = 0,63). The heterozygous genotype of rs2595104 had the highest frequency compared to the other genotypes in both groups. In case of the rs6584555 SNP the homozygous genotype of the major allele (TT) had the highest frequency in both groups (0.59). The frequency of homozygous genotype for risk allele had the lowest frequency for both SNPs [rs2595104 (AA): 0.19 in patients, 0.12 in controls; rs6584555 (CC): 0.05 in patients, 0.03 in controls]. We did not find significant association between SNP rs2595104 and rs6584555 andAF. We performed a protein-protein network analysis to assess functional connection among the protein products. The proteins coded by PITX2 and NEURL1 are connected indirectly via CTNNB1 and either JAG1 or DLL4 proteins. These interactive proteins are components of two major channels of cell communication pathways, the Wnt and Notch signaling pathways.