Cuesta-Llavona Elías, Lorca Rebeca, Rolle Valeria, Alonso Belén, Iglesias Sara, Rodríguez-Reguero Julian, Duarte-Herrera Israel David, Pérez-Oliveira Sergio, Junco-Vicente Alejandro, Lago Claudia García, Coto Eliecer, Gómez Juan
Hospital Universitario Central de Asturias (HUCA), 33011 Oviedo, Spain.
Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain.
Life (Basel). 2022 May 30;12(6):818. doi: 10.3390/life12060818.
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.
在大约40%-60%的肥厚型心肌病（HCM）病例中，未发现致病变异。我们的目的是评估长链非编码RNA（lncRNAs）与发生HCM风险之间的可能关联。方法：我们通过二代测序（NGS）对发现队列（238例HCM患者和212例对照）中10个已与心血管疾病相关的lncRNAs编码基因进行测序，并在验证队列（962例HCM患者和923例对照）中对rs74035787 G>A和rs1424019 A>G多态性进行基因分型。最后，我们通过桑格测序对FENDRR启动子进行测序。结果：通过NGS我们观察到，在我们的队列中FENDRR rs39527、rs39529和rs40384多态性与HCM显著相关（p = 0.0284；OR：0.24，95%CI：0.07-0.86）。通过对rs74035787多态性进行基因分型证实了NGS结果（p = 0.001；OR：0.38，95%CI：0.21-0.66）。此外，按性别分层（p = 0.003；OR：0.20，95%CI：0.06-0.53）和年龄（≥50岁，p = 0.001，OR：0.33，95%CI：0.16-0.63）时也存在关联。此外，在老年受试者中，rs1424019多态性GG基因型携带者发生HCM的风险显著高于AA/AG基因型携带者（p = 0.045，OR：1.24，95%CI：1.01-1.53）。另一方面，我们观察到rs74035787 A/rs1424019 G单倍型频率存在显著差异（p = 0.0035；OR：0.20，95%CI：0.07-0.59）。结论：我们的研究表明FENDRR基因变异与HCM之间存在显著关联。
