Sahin Sezgin, Romano Micol, Guzel Ferhat, Piskin David, Poddighe Dimitri, Sezer Siren, Kasapcopur Ozgur, Appleton C Thomas, Yilmaz Ilker, Demirkaya Erkan
Department of Paediatric Rheumatology, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey.
Division of Paediatric Rheumatology, Department of Paediatrics, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada.
Life (Basel). 2022 Apr 25;12(5):631. doi: 10.3390/life12050631.
Cardiovascular disease (CVD) remains underestimated in familial Mediterranean fever-associated AA amyloidosis (FMF-AA). We aimed to compare early markers of endothelial dysfunction and atherosclerosis in FMF-AA with a homozygous M694V mutation (Group 1 = 76 patients) in the Mediterranean fever (MEFV) gene and in patients with other genotypes (Group 2 = 93 patients). Measures of increased risk for future CVD events and endothelial dysfunction, including flow-mediated dilatation (FMD), pentraxin-3 (PTX3), and carotid intima-media thickness (cIMT), and fibroblast growth factor 23 (FGF23) as a marker of atherosclerotic vascular disease were compared between groups. The frequency of clinical FMF manifestations did not differ between the two groups apart from arthritis (76.3% in Group 1 and 59.1% in Group 2, p < 0.05). FMD was significantly lower in Group 1 when compared with Group 2 (MD [95% CI]: −0.6 [(−0.89)−(−0.31)]). cIMT, FGF23, and PTX3 levels were higher in Group 1 (cIMT MD [95% CI]: 0.12 [0.08−0.16]; FGF23 MD [95% CI]: 12.8 [5.9−19.6]; PTX3 MD [95% CI]: 13.3 [8.9−17.5]). In patients with FMF-AA, M694V homozygosity is associated with lower FMD values and higher cIMT, FGF23, and PTX3 levels, suggesting increased CVD risk profiles. These data suggest that a genotype−phenotype association exists in terms of endothelial dysfunction and atherosclerosis in patients with FMF-AA.
在家族性地中海热相关的AA淀粉样变性（FMF-AA）中，心血管疾病（CVD）仍未得到充分认识。我们旨在比较地中海热（MEFV）基因中纯合M694V突变的FMF-AA患者（第1组 = 76例患者）与其他基因型患者（第2组 = 93例患者）的内皮功能障碍和动脉粥样硬化早期标志物。比较了两组未来CVD事件风险增加和内皮功能障碍的指标，包括血流介导的血管舒张（FMD）、五聚素3（PTX3）、颈动脉内膜中层厚度（cIMT），以及作为动脉粥样硬化性血管疾病标志物的成纤维细胞生长因子23（FGF23）。除关节炎外，两组临床FMF表现的频率无差异（第1组为76.3%，第2组为59.1%，p < 0.05）。与第2组相比，第1组的FMD显著降低（MD [95% CI]：−0.6 [（−0.89）−（−0.31）]）。第1组的cIMT、FGF23和PTX3水平较高（cIMT MD [95% CI]：0.12 [0.08−0.16]；FGF23 MD [95% CI]：12.8 [5.9−19.6]；PTX3 MD [95% CI]：13.3 [8.9−17.5]）。在FMF-AA患者中，M694V纯合性与较低的FMD值以及较高的cIMT、FGF23和PTX3水平相关，提示CVD风险增加。这些数据表明，在FMF-AA患者的内皮功能障碍和动脉粥样硬化方面存在基因型-表型关联。
