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Rare Genetic Variants in Gata Transcription Factors in Patients with Hypertrophic Cardiomyopathy
- Source :
- Journal of Investigative Medicine. 65:926-934
- Publication Year :
- 2017
- Publisher :
- SAGE Publications, 2017.
-
Abstract
- Hypertrophic cardiomyopathy (HCM) is a very heterogeneous disease. Although primarily caused by mutations in genes encoding sarcomeric proteins, other genes might explain that heterogeneity. Potential candidate genes are GATA transcription factors that regulate the expression of proteins associated with HCM. Exons of GATA2, GATA4, and GATA6 genes were sequenced in 212 patients with unrelated HCM previously analyzed for genes encoding the most frequently mutated sarcomeric proteins. Functional effects of variants were predicted by in silico analyses. 3 potentially pathogenic variants were identified: c.-77G>A in GATA2, p.Ala343Thr (rs370588269) in GATA4, and p.Pro555Ala (rs146243018) in GATA6. Multivariate analyses showed that angina was more frequent in patients carrying sarcomeric and GATA rare variants (55% vs 23.2% in non-carriers of GATA rare variants, OR (95% CI) 7.12 (1.23 to 41.27), p=0.029). Among patients without a known causal mutation, GATA rare variants were associated with a greater maximum posterior wall thickness (16.4±4.4 vs 14.0±3.1 mm in non-carriers, p=0.021). Thus, variants having a putative effect on GATA genes would alter the expression of their target genes and could modify the hypertrophic response. Therefore, although relatively infrequent in patients with HCM, they may represent a novel insight into the molecular mechanisms related to the pathogenesis of HCM.
- Subjects :
- Adult
Male
Sarcomeres
0301 basic medicine
Heterozygote
Biology
medicine.disease_cause
Polymorphism, Single Nucleotide
General Biochemistry, Genetics and Molecular Biology
Cohort Studies
Young Adult
03 medical and health sciences
Exon
GATA6 Transcription Factor
medicine
Animals
Humans
Gene
Aged
Genetics
Mutation
GATA6
Anthropometry
GATA4
GATA2
Hypertrophic cardiomyopathy
General Medicine
Cardiomyopathy, Hypertrophic
Middle Aged
medicine.disease
GATA4 Transcription Factor
Pedigree
GATA2 Transcription Factor
030104 developmental biology
Echocardiography
Spain
Case-Control Studies
Multivariate Analysis
GATA transcription factor
Female
Subjects
Details
- ISSN :
- 17088267 and 10815589
- Volume :
- 65
- Database :
- OpenAIRE
- Journal :
- Journal of Investigative Medicine
- Accession number :
- edsair.doi.dedup.....1a958632193dbc722b3dc2150b933925