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脂肪细胞脂肪酸结合蛋白(FABP4)作为预测地中海贫血综合征中代谢驱动的低度和器官损伤的潜在生物标志物。

Adipocyte fatty acid-binding protein (FABP4) as a potential biomarker for predicting metabolically driven low-grade and organ damage in thalassemia syndromes.

机构信息

Department of Internal Medicine, Faculty of Medicine, Fayoum University, Fayoum, Egypt.

Department of Clinical Pathology/Hematology & Transfusion Medicine, Faculty of Medicine, Fayoum University, P.O. Box: 63514, Fayoum, Egypt.

出版信息

Ann Hematol. 2024 Sep;103(9):3473-3482. doi: 10.1007/s00277-024-05886-7. Epub 2024 Jul 19.

Abstract

Adipocyte fatty acid-binding protein (A-FABP; FABP4) plays a significant role in the pathogenesis and progression of metabolically driven low-grade inflammation and organ damage. This study aimed to evaluate the performance of circulating FABP4 as a predictive and diagnostic biomarker for thalassemia-associated cardiometabolic events. This case-control study enrolled 50 adults with β-thalassemia and 30 age-, sex-, and body mass index-matched controls. Participants underwent a comprehensive evaluation, including complete blood count, liver and kidney function tests, serum blood glucose, lipid profile, and ferritin levels, pelviabdominal ultrasound, ECG, and echocardiography after taking a full medical history and conducting a clinical examination. Serum levels of FABP4 were measured using an Enzyme-Linked-Immunosorbent-Assay. The diagnostic performance of FABP4 was assessed using receiver operator characteristic (ROC) curve analysis to determine optimal values for excluding and confirming cardiometabolic metflammation. The thalassemia cohort exhibited a statistically significant higher concentration of FABP4 compared to the control group (p-value < 0.001). Positive correlations were found between FABP4 and ferritin serum levels above 800 or 1000 ug/L, as well as with ALT, TGS, and LDL (p-value < 0.05). Circulating FABP4 was identified as a statistically significant risk factor for thalassemia-associated cardiometabolic comorbidities (OR = 84.00, 95%CI:18.6-378.6, p-value < 0.001). ROC analysis determined that the FABP4 exclusionary cut-off value > 2.30 ng/ml could effectively discriminate between thalassemia-associated adverse metaflammation and controls, while the FABP4 confirmatory cut-off value was > 2.58 ng/ml. In conclusion, circulating FABP4 appears to be a potential risk factor for predicting progression to cardiometabolic events in thalassemia-associated adverse metaflammation. FABP4 holds promise as a diagnostic and prognostic biomarker for disease monitoring and risk stratification. Further validation through large-scale, multicenter, prospective studies is warranted.

摘要

脂肪细胞脂肪酸结合蛋白(A-FABP;FABP4)在代谢驱动的低度炎症和器官损伤的发病机制和进展中发挥重要作用。本研究旨在评估循环 FABP4 作为预测和诊断地中海贫血相关代谢性心血管事件的生物标志物的性能。这项病例对照研究纳入了 50 名β-地中海贫血成人和 30 名年龄、性别和体重指数匹配的对照组。参与者接受了全面评估,包括全血细胞计数、肝肾功能检查、血清血糖、血脂谱和铁蛋白水平、骨盆超声、心电图和超声心动图,同时记录了完整的病史并进行了临床检查。使用酶联免疫吸附测定法测量血清 FABP4 水平。使用接收器操作特征(ROC)曲线分析评估 FABP4 的诊断性能,以确定排除和确认代谢性心血管炎症的最佳值。与对照组相比,地中海贫血组的 FABP4 浓度明显更高(p 值<0.001)。FABP4 与血清铁蛋白水平>800 或>1000μg/L,以及 ALT、TGS 和 LDL 呈正相关(p 值<0.05)。循环 FABP4 被确定为与地中海贫血相关的代谢性心血管合并症的统计学显著危险因素(OR=84.00,95%CI:18.6-378.6,p 值<0.001)。ROC 分析确定,FABP4 排除截断值>2.30ng/ml 可有效区分地中海贫血相关的不良代谢炎症和对照组,而 FABP4 确认截断值>2.58ng/ml。总之,循环 FABP4 似乎是预测地中海贫血相关不良代谢炎症进展为代谢性心血管事件的潜在危险因素。FABP4 有望成为疾病监测和风险分层的诊断和预后生物标志物。需要通过大规模、多中心、前瞻性研究进行进一步验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f4b/11358176/3826c6c9fb0c/277_2024_5886_Fig1_HTML.jpg

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