Inorganic arsenic (iAs) exposure has been reported to have an impact on cardiovascular diseases (CVD). However, there is not much known about the cardiac tissue injury of CVD patients in relation to iAs exposure and potential role of single nucleotide polymorphisms (SNPs) of genes related to iAs metabolism, oxidative stress, endothelial dysfunction and inflammation which may play important roles in such CVD cases. In this dual center cross-sectional study, based on the exclusion and inclusion criteria, we have recruited 50 patients out of 270, who came from known arsenic-affected and- unaffected areas of mainly Chittagong, Dhaka and Rajshahi divisions of Bangladesh and underwent open-heart surgery at the selected centers during July 2017 to June 2018. We found that the patients from arsenic affected areas contained significantly higher average iAs concentrations in their urine (6.72 ± 0.54 ppb, P = 0.028), nail (529.29 ± 38.76 ppb, P < 0.05) and cardiac tissue (4.83 ± 0.50 ppb, P < 0.05) samples. Patients’ age, sex, BMI, hypertension and diabetes status adjusted analysis showed that patients from arsenic-affected areas had significantly higher iAs concentration in cardiac tissue (2.854, 95%CI 1.017–8.012, P = 0.046) reflecting higher cardiac tissue injury among them (1.831, 95%CI 1.032–3.249, P = 0.039), which in turn allowed the analysis to assume that the iAs exposure have played a vital role in patients’ disease condition. Adjusted analysis showed significant association between urinary iAs concentration with AA (P = 0.012) and AG (P = 0.034) genotypes and cardiac iAs concentration with AA (P = 0.017) genotype of AS3MT rs10748835. The AG genotype of AS3MT rs10748835 (13.333 95%CI 1.280–138.845, P = 0.013), AA genotype of NOS3 rs3918181 (25.333 95%CI 2.065–310.757, P = 0.002), GG genotype of ICAM1 rs281432 (12.000 95%CI 1.325–108.674, P = 0.010) and AA genotype of SOD2 rs2758331 (13.333 95%CI 1.280–138.845, P = 0.013) were found significantly associated with CVD patients from arsenic-affected areas. Again, adjusted analysis showed significant association of AA genotype of AS3MT rs10748835 with CVD patients from arsenic affected areas. In comparison to the reference genotypes of the selected SNPs, AA of AS3MT 10748835, AG of NOS3 rs3918181 and AC of rs3918188, GG of ICAM1 rs281432, TT of VCAM1 rs3176867, AA of SOD2 rs2758331 and GT of APOE rs405509 significantly increased odds of cardiac tissue injury of CVD patients from arsenic affected areas. The results showed that the selected SNPs played a susceptibility role towards cardiac tissue iAs concentration and injury among CVD patients from iAs affected areas.

Background: Exposure to inorganic arsenic (iAs) through drinking water is currently a serious threat to public health of millions of people worldwide including Bangladesh. Some recent studies have shown that telomere dysfunction is emerging as an important factor in the pathogenesis of different cardiovascular diseases. Arsenic plays significant role on telomere dysfunction by altering the expression of telomere-related genes. The study was aimed to investigate the effects of arsenic on hTERT mRNA levels and their combined role in increasing CVD susceptibility. Methods: In  this cross sectional study, total of 50 CVD patients who underwent open heart surgery were recruited for this study. Urine, nail and cardiac tissue samples were collected and analyzed for As. Blood samples were quantified for hTERT expression analysis using real-time polymerase chain reaction. Results: The hTERT mRNA expression was found approx. 10 fold higher in the As-exposed patients than the As-unexposed patients (p<0.01). A strong positive correlation (p<0.01, R>0.3) was found between the hTERT mRNA levels and As contents in the cardiac tissue, nail and urine samples of the study subjects. The significant increase (approx. 4 fold) in the hTERT mRNA expression was found in the patients with coronary artery disease (CAD) than the non-CAD patients. Conclusions: The results of the study suggest that arsenic exposure increases hTERT mRNA expression which may in turn modify As-induced cardiovascular outcomes. The findings of this study will help to look deep into the association of As exposure in cardiovascular disease pathogenesis to open a new window in the diagnosis and treatment procedure of CVD. Bangladesh Med Res Counc Bull 2019; 45: 03-10

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