Effect of Arsenic Exposure on Human Telomerase Reverse Transcriptase (hTERT) Gene Expression and Telomere Length in Cardiovascular Disease Susceptibility

Abstract

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 As-induced 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.