Risk of carotid atherosclerosis associated with genetic polymorphisms of apolipoprotein E and inflammatory genes among arsenic exposed residents in Taiwan

Arsenic Exposure and Subclinical Endpoints of Cardiovascular Disease

“…A total of 360 SNPs and 18 genes were genotyped, and the investigators identified novel single nucleotide polymorphisms (SNPs) in ICAM-1 and VCAM-1 that had significant interactions with well-water arsenic in CVD risk which remained robust after adjustment for multiple testing [94]. Regarding subclinical cardiovascular endpoints, the majority of evidence comes from a series of studies conducted in Taiwan that found the prevalence of arsenic-related carotid atherosclerosis was modifiable by genetic polymorphisms related to oxidative stress, inflammation, and arsenic metabolism [95-99]. However, these studies have included a limited number of genetic variants and did not have enough sample size to evaluate the effect-modification at low levels of exposure.…”

Arsenic and the Cardiovascular System

“…Residents who had been exposed to high levels of As (>50 μg/L) had an age-and gender-adjusted odds ratio (OR) of 3.3 for developing carotid atherosclerosis while those who had been exposed to low (≤10 μg/L) and mid-levels (10.1-50 μg/L) of As had an OR of 1.0 and 1.4, respectively [60]. Similarly, Hsieh and co-workers also showed a dose-dependent relationship between As exposure and increased risk of carotid atherosclerosis in Taiwan [61]. Residents who had been exposed to high levels of As in drinking water (≥50 μg/L) with a cumulative arsenic exposure (CAE) of ≥1.1 mg/L/year had an age-and gender-adjusted OR of 2.4 and 1.9 for developing carotid atherosclerosis, respectively (p < 0.05).…”

“…On similar lines, polymorphism within lipid metabolism and inflammation genes has also been shown to be linked to CVD. The relationship of polymorphism in APOE (lipid metabolism gene) and MCP-1 (inflammation gene) with the risk of carotid atherosclerosis was evaluated in 479 arsenic-exposed residents of Taiwan [61]. Residents with a carotid artery IMT thickness of ≥1.0 mm or with observable plaque in the extra-cranial carotid artery were diagnosed as having carotid arteriosclerosis.…”

Interaction between arsenic exposure from drinking water and genetic susceptibility in carotid intima–media thickness in Bangladesh

“…Epidemiologic evidence suggests a positive association between As exposure and cIMT [2]. In addition, some studies indicate that genetic factors could modify the cardiovascular effects of As exposure [3-7]. However, existing studies have limitations such as a small number of clinical cases of CVD and the inclusion of a limited number of genetic variants.…”

“…Thus, in addition to genetic variants related to As metabolism, those involved in these mechanisms such as heme oxygenase 1 ( HMOX1 ), nitric oxide synthase 3 ( NOS3 ), superoxide dismutase 2 ( SOD2 ), alpha polypeptide ( CYBA ), apolipoprotein E ( APOE ), tumor necrosis factor ( TNF ), interleukin 6 ( IL6 ), intercellular adhesion molecule 1 ( ICAM1 ), sphingosine-1-phosphate receptor 1 ( S1PR1 ), and vascular cell adhesion molecule 1 ( VCAM1 ) may also modify the cardiovascular effects of As exposure. A few studies in Taiwan have investigated whether As-induced carotid atherosclerosis can be modified by polymorphisms in HMOX1 , NOS3 , SOD2 , CYBA , and APOE genes [3, 6, 7]. However, larger studies with a comprehensive selection of SNPs are needed to confirm the findings.…”