title: Rare genetic variants in GATA transcription factors in patients with hypertrophic cardiomyopathy.
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 ofGATA2,GATA4, andGATA6genes 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 inGATA2, p.Ala343Thr (rs370588269) inGATA4, and p.Pro555Ala (rs146243018) inGATA6Multivariate 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.
authors.affiliation: Bone and Mineral Research Unit, Instituto Reina Sofía de Investigación, Hospital Universitario Central de Asturias, Oviedo, Spain.|Red de Investigación Renal REDinREN from Instituto de Salud Carlos III, Oviedo, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Alonso-Montes
authors.affiliation: Red de Investigación Renal REDinREN from Instituto de Salud Carlos III, Oviedo, Spain.|Cardiology Department, Fundación Asturcor, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Rodríguez-Reguero
authors.affiliation: Red de Investigación Renal REDinREN from Instituto de Salud Carlos III, Oviedo, Spain.|Cardiology Department, Fundación Asturcor, Hospital Universitario Central de Asturias, Oviedo, Spain.|Molecular Genetics Unit, Instituto Reina Sofía de Investigación, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Martín
authors.affiliation: Red de Investigación Renal REDinREN from Instituto de Salud Carlos III, Oviedo, Spain.|Universidad de Oviedo, Oviedo, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Gómez
authors.affiliation: Red de Investigación Renal REDinREN from Instituto de Salud Carlos III, Oviedo, Spain.|Molecular Genetics Unit, Instituto Reina Sofía de Investigación, Hospital Universitario Central de Asturias, Oviedo, Spain.|Universidad de Oviedo, Oviedo, Spain.
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.affiliation: Bone and Mineral Research Unit, Instituto Reina Sofía de Investigación, Hospital Universitario Central de Asturias, Oviedo, Spain.|Red de Investigación Renal REDinREN from Instituto de Salud Carlos III, Oviedo, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Naves-Díaz
authors.affiliation: Red de Investigación Renal REDinREN from Instituto de Salud Carlos III, Oviedo, Spain.|Cardiology Department, Fundación Asturcor, Hospital Universitario Central de Asturias, Oviedo, Spain.|Molecular Genetics Unit, Instituto Reina Sofía de Investigación, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: César
authors.initials: C
authors.lastname: Morís
authors.affiliation: Bone and Mineral Research Unit, Instituto Reina Sofía de Investigación, Hospital Universitario Central de Asturias, Oviedo, Spain.|Red de Investigación Renal REDinREN from Instituto de Salud Carlos III, Oviedo, Spain.|Molecular Genetics Unit, Instituto Reina Sofía de Investigación, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Jorge B
authors.initials: JB
authors.lastname: Cannata-Andía
authors.affiliation: Bone and Mineral Research Unit, Instituto Reina Sofía de Investigación, Hospital Universitario Central de Asturias, Oviedo, Spain.|Red de Investigación Renal REDinREN from Instituto de Salud Carlos III, Oviedo, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Rodríguez
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000886:Anthropometry; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D004452:Echocardiography; D005260:Female; D050989:GATA2 Transcription Factor / Q000235:genetics*; D050991:GATA4 Transcription Factor / Q000235:genetics*; D050993:GATA6 Transcription Factor / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012518:Sarcomeres / Q000378:metabolism; D013030:Spain; D055815:Young Adult
chemical_list: D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human
keywords: Cardiomyopathies; Genotype; Polymorphism, Genetic