Singh Mable Misha, Kumar Ravindra, Tewari Satyendra, Agarwal Sarita
a Department of Medical Genetics , Sanjay Gandhi Postgraduate Institute of Medical Sciences , Lucknow , India.
b Division of Genetic Disorders , ICMR-National Institute for Research in Tribal Health , Jabalpur , India.
Hematology. 2019 Dec;24(1):20-25. doi: 10.1080/10245332.2018.1502397. Epub 2018 Aug 10.
Cardiomyocytes are particularly susceptible to complications from iron loading. The blood transfusions in thalassaemia major create loading of iron that cannot be naturally excreted. Apolipoprotein E and Glutathione S-transferase act as the scavenger of free radicals, which are generated due to excess iron. The variants of Apolipoprotein E (ApoE) and Glutathione S-transferase (GST) may play a role in oxidative damage-induced cardiomyopathy, so we aimed to study the association of genetic variants of these genes on diastolic dysfunction in our patients.
One hundred and five β-thalassaemia patients older than 10 years were enrolled for the study. Two-dimensional and M-mode echocardiography analysis was done in all patients. Genotyping of the genetic variants of aforementioned genes was done using the PCR-RFLP method. Serum Glutathione S-transferase levels were estimated by ELISA.
Diastolic dysfunction was observed in 24 (22.8%) patients, whereas left ventricular hypertrophy was present in 37(35.2%) patients. There was a significant association of GSTM1 null allele with diastolic dysfunction only. Serum GST levels were also positively correlated with e/a and e/e' ratio. Positive association of ApoE E2 allele with the diastolic dysfunction was also seen.
Patients having Glutathione S-transferase M1 allele and Apolipoprotein E E2 allele are predisposed to oxidative stress-induced cardiac injury.
心肌细胞对铁负荷引起的并发症特别敏感。重型地中海贫血患者的输血会导致铁负荷增加，而铁无法自然排出。载脂蛋白E和谷胱甘肽S-转移酶作为自由基的清除剂，自由基是由过量铁产生的。载脂蛋白E（ApoE）和谷胱甘肽S-转移酶（GST）的变体可能在氧化损伤诱导的心肌病中起作用，因此我们旨在研究这些基因的遗传变体与我们患者舒张功能障碍之间的关联。
招募了105名年龄超过10岁的β地中海贫血患者进行研究。对所有患者进行二维和M型超声心动图分析。使用PCR-RFLP方法对上述基因的遗传变体进行基因分型。通过ELISA估计血清谷胱甘肽S-转移酶水平。
24名（22.8%）患者出现舒张功能障碍，而37名（35.2%）患者存在左心室肥厚。仅GSTM1无效等位基因与舒张功能障碍有显著关联。血清GST水平也与e/a和e/e'比值呈正相关。还观察到ApoE E2等位基因与舒张功能障碍呈正相关。
具有谷胱甘肽S-转移酶M1等位基因和载脂蛋白E E2等位基因的患者易发生氧化应激诱导的心脏损伤。
