Association of arsenic-induced cardiovascular disease susceptibility with genetic polymorphisms

Abstract

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.

Hair Lead, Aluminum, and Other Toxic Metals in Normal-Weight and Obese Patients with Coronary Heart Disease

“…The effects of As exposure on CVD and CHD in particular was shown to be dose-dependent [40]. A significant influence of AS3MT, NOS3, ICAM1, VCAM1, SOD2, and APOE gene polymorphisms on the interaction between As exposure and CHD was demonstrated [41].…”

Arsenic exposure and non-carcinogenic health effects

“…They also showed a significant correlation between the accumulation of iAs and As3MT, nitric oxide synthase (NOS3), intercellular adhesion molecule-1 (ICAM1), and superoxide dismutase (SOD2) genotypes. 256 A retrospective study in a Chilean population found for the medium exposure categories (60–623 μg/L) and higher (>623 μg/L), a hypertension OR of 1.49 (95% CI: 1.09; 2.05) and 1.65 (95% CI 1.18, 2.32), respectively. Similar results were observed when analyzing cumulative lifetime exposure.…”

“…Several epidemiological studies have showed the link between chronic arsenic ingestion and various cardiovascular disorders, including peripheral vascular disease, ischemic heart disease, aterosclerosis, 255 and hypertension. 256,257 A study evaluated the association of mean arsenic concentrations (<1 and 118 μg/L) in drinking water with cardiovascular mortality in the Spanish population. Compared with the total Spanish population, cardiovascular mortality rates increased in municipalities with arsenic drinking water concentrations >10 μg/L.…”

“…Several epidemiological studies have showed the link between chronic arsenic ingestion and various cardiovascular disorders, including peripheral vascular disease, ischemic heart disease, aterosclerosis, 255 and hypertension. 256,257…”

Arsenic Exposure through Dietary Intake and Associated Health Hazards in the Middle East

“…Long-term exposure to high levels of iAs in drinking water has been linked with skin disorders and increased risk of diabetes, high blood pressure, and several types of cancer. iAs and As compounds are considered to be carcinogenic [ 36 , 37 ].…”