内皮素-1 基因多态性（G8002A）与内皮单核细胞激活肽 II：在β-重型地中海贫血患儿血管功能障碍中的作用。

Endothelin-1 gene polymorphism (G8002A) and endothelial monocyte-activating polypeptide II: Role in vascular dysfunction in pediatric patients with β-thalassemia major.

机构信息

Pediatric Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

Pediatric Department, Military Medical Services and Military Medical Academy, Cairo, Egypt.

出版信息

Cytokine. 2023 Jan;161:156048. doi: 10.1016/j.cyto.2022.156048. Epub 2022 Oct 21.

DOI:10.1016/j.cyto.2022.156048

PMID:36279697

Abstract

BACKGROUND

Endothelin-1 (ET-1), a potent endogenous vasoconstrictor, stimulates production of reactive oxygen species. Endothelial monocyte-activating polypeptide-II (EMAP-II) is a multifunctional polypeptide.

AIM

To assess ET-1 gene polymorphism (G8002A) in pediatric patients with β-thalassemia major (β-TM) as a potential genetic marker for vascular dysfunction and its possible relation to EMAP II, oxidative stress and vascular complications.

METHODS

β-TM patients (n = 95) without symptomatic cardiac or renal disease were compared with 95 healthy controls. Markers of hemolysis, serum ferritin, urinary albumin-to-creatinine ratio, serum EMAP II, malondialdehyde (MDA) and antioxidant enzymes; superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH), glutathione reductase and catalase were measured. ET-1 gene polymorphism (G8002A) was determined using polymerase chain reaction‑restriction fragment length polymorphism.

RESULTS

β-TM patients had significantly higher EMAP II than healthy controls. EMAP II was significantly higher among patients with cardiac disease, pulmonary hypertension (PH) risk, nephropathy, poor compliance to therapy and ferritin ≥ 2500 μg/L. There were significant correlations between EMAP II and transfusion index, LDH, ferritin and oxidative stress markers. The AA genotype of ET-1 gene polymorphism (G8002A) was significantly higher among β-TM patients than controls. The number of patients with cardiac disease, PH risk or nephropathy was significantly higher among AA genotype compared with GG and GA genotypes. Lactate dehydrogenase (LDH), serum ferritin, EMAP II, MDA, SOD and GPx were significantly higher in AA genotype.

CONCLUSION

ET-1 gene polymorphism (G8002A) could be a possible genetic marker for prediction of increased susceptibility to cardiopulmonary and renal complications among pediatric patients with β-TM.

摘要

背景

内皮素-1（ET-1）是一种有效的内源性血管收缩剂，可刺激活性氧的产生。内皮单核细胞激活肽-II（EMAP-II）是一种多功能多肽。

目的

评估小儿重型β地中海贫血（β-TM）患者的 ET-1 基因多态性（G8002A），作为血管功能障碍的潜在遗传标志物，及其与 EMAP II、氧化应激和血管并发症的可能关系。

方法

比较无心脏或肾脏疾病症状的β-TM 患者（n=95）与 95 名健康对照者。测定溶血标志物、血清铁蛋白、尿白蛋白/肌酐比值、血清 EMAP II、丙二醛（MDA）和抗氧化酶；超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）、还原型谷胱甘肽（GSH）、谷胱甘肽还原酶和过氧化氢酶。采用聚合酶链反应-限制性片段长度多态性测定 ET-1 基因多态性（G8002A）。

结果

β-TM 患者的 EMAP II 显著高于健康对照组。患有心脏病、肺动脉高压（PH）风险、肾病、治疗依从性差和铁蛋白≥2500μg/L 的患者 EMAP II 显著升高。EMAP II 与输血指数、LDH、铁蛋白和氧化应激标志物呈显著相关。ET-1 基因多态性（G8002A）AA 基因型在β-TM 患者中显著高于对照组。与 GG 和 GA 基因型相比，AA 基因型患者中患有心脏病、PH 风险或肾病的患者数量明显更多。AA 基因型的乳酸脱氢酶（LDH）、血清铁蛋白、EMAP II、MDA、SOD 和 GPx 显著升高。