Junco-Vicente Alejandro, Solache-Berrocal Guillermo, Del Río-García Álvaro, Rolle-Sóñora Valeria, Areces Sheila, Morís César, Martín María, Rodríguez Isabel
Department of Cardiology, Área del Corazón, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain.
Cardiac Pathology Research Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.
Front Cardiovasc Med. 2022 Oct 20;9:989539. doi: 10.3389/fcvm.2022.989539. eCollection 2022.
Aortic valve stenosis is the most frequent valve disease in developed countries and its prevalence will increase with population aging. There is still no pharmaceutical treatment nor biomarker to determine the susceptibility to develop aortic stenosis. Therefore, we analyzed the association of polymorphisms in risk loci with calcific aortic stenosis. Patients with aortic valve disease were genotyped for rs6702619, rs10455872, and rs1800795 polymorphisms and circulating levels of interleukin-6 (IL-6) were measured. Calcium content of leaflets obtained in valve replacement surgeries was determined by micro-computed tomography. In the genotyping of 578 individuals, we found significant association between and polymorphisms and aortic stenosis in patients with tricuspid aortic valve, independently of other potentially confounding variables such as age and dyslipidemia. There was no association of these polymorphisms with valve calcium content, but this value correlated with the mean aortic pressure gradient ( = 0.44; < 0.001). The CC genotype of polymorphism was associated with higher levels of serum IL-6 compared to other genotypes (23.5 vs. 10.5 pg/ml, respectively; = 0.029). Therefore, patients carrying the CC genotype of rs1800795 polymorphism present higher levels of circulating IL-6 and this could contribute to the severity of the aortic valve stenosis. Our results agree with the identification of as a locus risk for stenosis and also with the intervention of this cytokine in aortic valve calcification. A more exhaustive follow-up of those patients carrying risk genotypes is therefore recommended.
在发达国家,主动脉瓣狭窄是最常见的瓣膜疾病,并且其患病率会随着人口老龄化而增加。目前仍然没有药物治疗方法,也没有生物标志物可用于确定发生主动脉狭窄的易感性。因此,我们分析了风险基因座中的多态性与钙化性主动脉狭窄之间的关联。对患有主动脉瓣疾病的患者进行rs6702619、rs10455872和rs1800795多态性的基因分型,并测量白细胞介素-6(IL-6)的循环水平。通过微型计算机断层扫描确定瓣膜置换手术中获取的瓣叶的钙含量。在对578名个体进行基因分型时,我们发现,在患有三尖瓣主动脉瓣的患者中,rs6702619和rs1800795多态性与主动脉狭窄之间存在显著关联,且独立于其他潜在的混杂变量,如年龄和血脂异常。这些多态性与瓣膜钙含量无关联,但该值与平均主动脉压力梯度相关(r = 0.44;P < 0.001)。与其他基因型相比,rs1800795多态性的CC基因型与更高的血清IL-6水平相关(分别为23.5 vs. 10.5 pg/ml;P = 0.029)。因此,携带rs1800795多态性CC基因型的患者循环IL-6水平较高,这可能导致主动脉瓣狭窄的严重程度增加。我们的结果与将rs1800795鉴定为狭窄的风险基因座一致,也与这种细胞因子在主动脉瓣钙化中的作用一致。因此,建议对那些携带风险基因型的患者进行更详尽的随访。