Life (May 2022)

Association of the Genetic Variation in the Long Non-Coding RNA FENDRR with the Risk of Developing Hypertrophic Cardiomyopathy

  • Elías Cuesta-Llavona,
  • Rebeca Lorca,
  • Valeria Rolle,
  • Belén Alonso,
  • Sara Iglesias,
  • Julian Rodríguez-Reguero,
  • Israel David Duarte-Herrera,
  • Sergio Pérez-Oliveira,
  • Alejandro Junco-Vicente,
  • Claudia García Lago,
  • Eliecer Coto,
  • Juan Gómez

DOI
https://doi.org/10.3390/life12060818
Journal volume & issue
Vol. 12, no. 6
p. 818

Abstract

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Background: In around 40–60% of Hypertrophic Cardiomyopathy (HCM) cases pathogenic variants are not identified. Our aim was to evaluate the possible association of lncRNAs with the risk of developing HCM. Methods: We sequenced 10 lncRNAs coding genes that have been associated with cardiovascular disease in a discovery cohort (238 HCM patients and 212 controls) by NGS, and genotyped rs74035787 G>A and rs1424019 A>G polymorphism in a validation cohort (962 HCM patients and 923 controls). Finally, we sequenced the FENDRR promoter by Sanger sequencing. Results: We observed by NGS that FENDRR rs39527, rs39529 and rs40384 polymorphisms were significantly associated with HCM in our cohort (p = 0.0284; OR: 0.24, 95%CI: 0.07–0.86). NGS results were confirmed by genotyping rs74035787 polymorphism (p = 0.001; OR:0.38, 95%CI: 0.21–0.66). Moreover, it is also associated when stratification by sex (p = 0.003; OR:0.20, 95%CI: 0.06–0.53), and age (≥50 years old p = 0.001, OR:0.33, 95%CI: 0.16–0.63) Moreover, the risk of HCM in the carriers of the GG genotype of the rs1424019 polymorphism was significantly higher than that of the AA/AG genotypes carriers in the elderly subjects (p = 0.045, OR:1.24, 95%CI: 1.01–1.53). On the other hand, we observed significant differences in the rs74035787 A/rs1424019 G haplotype frequency (p = 0.0035; OR: 0.20, 95%CI: 0.07–0.59). Conclusions: Our study suggested a significant association between FENDRR gene variants and HCM.

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