Missense mutations in the CITED2 gene may contribute to congenital heart disease.
Humans
Heart Defects, Congenital
/ genetics
Genetic Predisposition to Disease
Female
Polymorphism, Single Nucleotide
Case-Control Studies
Repressor Proteins
/ genetics
Male
Mutation, Missense
Trans-Activators
/ genetics
Phenotype
Gene Frequency
Homozygote
Infant
Heterozygote
DNA Mutational Analysis
Child, Preschool
Risk Factors
Genetic Association Studies
Child
China
/ epidemiology
Adolescent
Allele-specific PCR
CITED2 gene
Congenital heart disease (CHD)
Genotype
Sequencing
Single nucleotide polymorphism (SNP)
Journal
BMC cardiovascular disorders
ISSN: 1471-2261
Titre abrégé: BMC Cardiovasc Disord
Pays: England
ID NLM: 100968539
Informations de publication
Date de publication:
27 Sep 2024
27 Sep 2024
Historique:
received:
15
03
2024
accepted:
08
07
2024
medline:
28
9
2024
pubmed:
28
9
2024
entrez:
28
9
2024
Statut:
epublish
Résumé
Congenital heart disease (CHD) is a lifelong abnormality present from birth. Multiple studies have shown that mutations in genes involved in heart development could cause congenital heart disease. The CITED2 gene works as a transcription factor in the hypoxic pathway for the development of the heart. Therefore, five CHD types, ventricular septal defect, atrial septal defect, atrioventricular septal defect, tetralogy of fallot, and patent ductus arteriosus, were evaluated by conducting a targeted single nucleotide polymorphism (SNP) analysis of the CITED2 gene variant rs375393125 (T > C). This study aimed to identify the association of CITED2 gene mutations in CHD patients. Three hundred fifty samples, 250 from patients and 100 from controls, were collected for this genetic analysis. Allele-specific PCR and gel electrophoresis were used to identify the target missense mutations. The genotypic results of the CHDs were further validated through Sanger sequencing. The frequency of the homozygous mutant (CC) in CHD patients was 48.4%, and of the heterozygous mutant (TC) genotype was 11.4%; these percentages are higher than controls (1%). The control samples had only one heterozygous TC and no homozygous CC genotype. The chi-square value was obtained at 103.9 with a probability of 0.05, more significant than the significance value of 21.03. The odds ratio was 43.7, which is > 1. The calculated value of ANOVA was 11.6, which was more significant than the F critical value of 3.7. As a result of sequencing, the mutant sample of each selected CHD type was found heterozygous or homozygous, and the results were like those obtained through conventional PCR. The samples of CHD patients showed mutations. Therefore, the CITED2 gene SNP might be associated with CHD.
Sections du résumé
BACKGROUND
BACKGROUND
Congenital heart disease (CHD) is a lifelong abnormality present from birth. Multiple studies have shown that mutations in genes involved in heart development could cause congenital heart disease. The CITED2 gene works as a transcription factor in the hypoxic pathway for the development of the heart. Therefore, five CHD types, ventricular septal defect, atrial septal defect, atrioventricular septal defect, tetralogy of fallot, and patent ductus arteriosus, were evaluated by conducting a targeted single nucleotide polymorphism (SNP) analysis of the CITED2 gene variant rs375393125 (T > C). This study aimed to identify the association of CITED2 gene mutations in CHD patients.
METHODS
METHODS
Three hundred fifty samples, 250 from patients and 100 from controls, were collected for this genetic analysis. Allele-specific PCR and gel electrophoresis were used to identify the target missense mutations. The genotypic results of the CHDs were further validated through Sanger sequencing.
RESULTS
RESULTS
The frequency of the homozygous mutant (CC) in CHD patients was 48.4%, and of the heterozygous mutant (TC) genotype was 11.4%; these percentages are higher than controls (1%). The control samples had only one heterozygous TC and no homozygous CC genotype. The chi-square value was obtained at 103.9 with a probability of 0.05, more significant than the significance value of 21.03. The odds ratio was 43.7, which is > 1. The calculated value of ANOVA was 11.6, which was more significant than the F critical value of 3.7. As a result of sequencing, the mutant sample of each selected CHD type was found heterozygous or homozygous, and the results were like those obtained through conventional PCR.
CONCLUSION
CONCLUSIONS
The samples of CHD patients showed mutations. Therefore, the CITED2 gene SNP might be associated with CHD.
Identifiants
pubmed: 39333893
doi: 10.1186/s12872-024-04035-2
pii: 10.1186/s12872-024-04035-2
doi:
Substances chimiques
CITED2 protein, human
0
Repressor Proteins
0
Trans-Activators
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
516Informations de copyright
© 2024. The Author(s).
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