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Rare genetic variants in GATA transcription factors in patients with hypertrophic cardiomyopathy
  1. Cristina Alonso-Montes1,2,
  2. Julián Rodríguez-Reguero2,3,
  3. María Martín2,3,4,
  4. Juan Gómez2,5,
  5. Eliecer Coto2,4,5,
  6. Manuel Naves-Díaz1,2,
  7. César Morís2,3,4,
  8. Jorge B Cannata-Andía1,2,4,
  9. Isabel Rodríguez1,2
  1. 1Bone and Mineral Research Unit, Instituto Reina Sofía de Investigación, Hospital Universitario Central de Asturias, Oviedo, Spain
  2. 2Red de Investigación Renal REDinREN from Instituto de Salud Carlos III, Oviedo, Spain
  3. 3Cardiology Department, Fundación Asturcor, Hospital Universitario Central de Asturias, Oviedo, Spain
  4. 4Molecular Genetics Unit, Instituto Reina Sofía de Investigación, Hospital Universitario Central de Asturias, Oviedo, Spain
  5. 5Universidad de Oviedo, Oviedo, Spain
  1. Correspondence to Dr Isabel Rodríguez, Bone and Mineral Research Unit, Hospital Universitario Central de Asturias, Edificio FINBA (N+1 F.2), Avda. de Roma s/n, Oviedo 33011, Spain; irodriguez{at}


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.

  • Cardiomyopathies
  • Polymorphism, Genetic
  • Genotype

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  • Contributors EC and IR contributed to the conception and design of the work. CA-M, JR-R, MM, JG, MN-D, CM, JBC-A, and IR contributed to the acquisition, analysis, or interpretation of data. CA-M and IR drafted the manuscript. JR-R, MM, JG, EC, MN-D, CM, and JBC-A revised the manuscript critically for important intellectual content. All the authors approved the final version to be published. All the authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

  • Funding This work was financed by Plan Nacional de I+D+i 2008–2011; Plan Estatal de I+D+i 2013–2016; Instituto de Salud Carlos III (ISCIII)–Fondo Europeo de Desarrollo Regional (FEDER) (PI07/0659, PI10/00173 and PI13/00497); Plan de Ciencia, Tecnología e Innovación 2013–2017 del Principado de Asturias (GRUPIN14–028); Instituto Reina Sofía de Investigación Nefrológica; Fundación Renal Íñigo Álvarez de Toledo; and Red de Investigación Renal-RedInRen from ISCIII (RD06/0016/1013 RD12/0021/1023 and RD16/0009/0017). CA-M and IR were financially supported by Fundación para el Fomento en Asturias de la Investigación Científica Aplicada y la Tecnología (FICYT).

  • Disclaimer The funders had no involvement in the study design; in the collection, analysis, and interpretation of the data; in the writing of the report; and in the decision to submit the paper for publication.

  • Competing interests None declared.

  • Ethics approval Ethics Committee for Clinical Investigation of Asturias.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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