砷暴露对心血管疾病易感性人群端粒酶逆转录酶基因表达和端粒长度的影响

Mohammad Al Forkan, Md Omar Hasan Chowdhury, Rahee Hasan Chowdhury, Fahmida Binta Wali, Amit Datta, Md Nezam Uddin, Md. Jibran Alam, L. Khaleda
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引用次数: 0

摘要

背景:受砷污染的地下水对人类健康的有害影响已在世界范围内得到报道。流行病学研究已经确定砷暴露与心血管疾病(CVD)风险的不良关联。端粒功能障碍正在成为各种心血管并发症发病机制的一个重要因素。目的:研究砷暴露对孟加拉国心血管病患者人端粒酶逆转录酶(hTERT)基因表达和端粒长度的影响。采集指甲样本并分析砷含量作为慢性暴露的生物标志物。从血液样本中提取的RNA和DNA分别用于hTERT表达分析和端粒长度测量,使用实时聚合酶链式反应。结果:来自已知砷影响区的患者(砷暴露患者组)显示hTERT基因的表达是来自已知砷未影响区(砷未暴露患者组的患者)的约9.7倍,端粒长度约1.4倍。我们发现hTERT表达(r=0.407,p=0.001)和端粒长度(r=0.437,p=0.003)与指甲样本中as浓度显著相关。在整个研究人群中,尤其是冠状动脉疾病(CAD)患者的hTERT基因表达是非CAD患者组的约3.4倍,端粒长度约1.5倍。结论:我们的研究结果表明,在孟加拉国砷暴露的CVD患者中,慢性砷暴露与hTERT表达和端粒长度的增加呈正相关,这种相关性反过来会影响长期砷暴露的心血管结果。我们还认为,Asinduced CVD可能采用不同于As-independent CVD的机制。这项研究的发现将为通过更深入的研究揭示砷诱导的CVD背后的机制铺平道路。2022年孟加拉医学研究会;48(1):56-63
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Effect of Arsenic Exposure on Human Telomerase Reverse Transcriptase (hTERT) Gene Expression and Telomere Length in Cardiovascular Disease Susceptibility
Background: The deleterious impact of arsenic (As) contaminated groundwater on human health has been reported worldwide. Epidemiological studies have identified adverse association of arsenic exposure with the risk of cardiovascular diseases (CVD). Telomere dysfunction is emerging as an important factor underlying the pathogenesis of various cardiovascular complications. Objective: The aim of the study was to investigate the effect of arsenic exposure on human telomerase reverse transcriptase (hTERT) gene expression and telomere length in arsenic-exposed cardiovascular disease patients of Bangladesh. Methods: A total of 53 CVD patients from known As-affected and unaffected areas of Bangladesh and subjected to open heart surgery were recruited. Nail samples were collected and analysed for arsenic content as a biomarker of chronic exposure. RNA and DNA extracted from blood samples were used for hTERT expression analysis and telomere length measurement respectively, using real-time polymerase chain reaction. Results: The patients from known As-affected areas (As-exposed patients group) showed approximately 9.7 fold higher expression of hTERT gene and approximately 1.4 fold higher telomere length than the patients from known As-unaffected areas (As-unexposed patients group). We found significant association of both hTERT expression (r= 0.407, p= 0.001) and telomere length (r=0.437, p=0.003) with as concentration in nail samples. Of the total study population, the coronary artery disease (CAD) patients in particular showed approximately 3.4 fold higher expression of hTERT gene and approximately 1.5 fold higher telomere length than the non-CAD patients group. Conclusion: Our findings suggest that chronic arsenic exposure is positively associated with increased hTERT expression and telomere length in As-exposed CVD patients of Bangladesh and that this association in turn can influence the cardiovascular outcomes of prolonged arsenic exposure. We also suggest that Asinduced CVD possibly adopts a mechanism that is different from that of As-independent CVD. Findings of this study will pave the way to unfold the mechanism behind As-induced CVD through more in-depth research. Bangladesh Med Res Counc Bull 2022; 48(1): 56-63         
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期刊介绍: The official publication of the Bangladesh Medical Research Council.
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