Abstract

Background: Despite the clear role of the Nkx2-5 gene mutations as the trigger for Congenital Heart Disease (CHD) in different populations, the condition of these mutations in our population remains obscure. Objectives: The present study aimed to assess different Nkx2-5 gene mutations in a sample of Iranian patients with CHD. Patients and Methods: This cross-sectional study was conducted on 79 consecutive suspected non-syndromic CHD patients at Rajaie Cardiovascular Medical and Research Center between 2016 and 2017. Detailed clinical evaluations were performed and CHD was confirmed by echocardiography. The exons of the Nkx2-5 gene were sequenced. In silico analysis was done using Mutation taster, SNP nexus, and Vienna RNA package. In addition, statistical analysis was performed using the SPSS statistical software, version 16.0. P ≤ 0.05 was considered to be statistically significant. Results: The study results revealed four synonymous polymorphisms; i.e., rs2277923, rs703752, rs3729753, and c.217C > T, the last of which was novel. Regarding the frequency of different Single Nucleotide Polymorphism (SNP) genotypes, the overall frequency of wild, heterozygous, and mutant genotypes was respectively 65.8%, 31.6%, and 2.5% for rs2277923, 54.4%, 0.0%, and 45.6% for rs703752, 96.2%, 3.8%, and 0.0% for rs3729753, and 93.7%, 6.3%, and 0.0% for c.217 C > T. Bioinformatics analysis demonstrated that the detected novel variants were not pathogens. Moreover, the genotypic variants of all SNPs were independent of gender, type of heart defect, and hereditary form of the disease. Conclusions: The results could not show any major roles for different exon-related SNPs on the Nkx2-5 gene as the candidate risk profile for CHD. The results also demonstrated no significant associations between such mutations and increased likelihood of specific heart defects.

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