Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

2011 ◽  
Vol 111 (6) ◽  
pp. 804-810 ◽  
Author(s):  
Yi-Chen Hsieh ◽  
Li-Ming Lien ◽  
Wen-Ting Chung ◽  
Fang-I Hsieh ◽  
Pei-Fan Hsieh ◽  
...  
2021 ◽  
Vol 25 (9) ◽  
pp. 1645-1652
Author(s):  
A.T. Adeboye ◽  
H.O. Awobode ◽  
A.S. Adebayo ◽  
J.R. Djouaka ◽  
R.D. Isokpehi ◽  
...  

Exposure to toxic inorganic Arsenic (iAs) in areas endemic for urogenital schistosomiasis may confer increased risk for bladder cancer. The severity of the adverse effects of iAs however depends on its metabolism, which is highly variable among individuals. Genetic polymorphism in Arsenic (+3) Methyl Transferase enzyme, accounts significantly for these variations. To investigate the relationship of AS3MT gene polymorphisms and Arsenic metabolism to schistosomiasis and/or associated bladder pathology, 119 individualsfrom Eggua in southwest Nigeria were recruited for this study. Screening for schistosomiasis and bladder pathology was done by microscopy and ultrasonography respectively. Wagtech Digital Arsenator was used to assess total urinary arsenic concentrations and thus determine the level of arsenic exposure. The single nucleotide polymorphism AS3MT/Met287Thr T>C (rs11191439) was genotyped using Alelle-Specific PCR. Of the participants who tested positive for schistosomiasis, 33.3% exhibited bladder pathology. Total urinary arsenic concentration in 80% of the participants was above the WHO limit of 0.05mg/L. The Met287Thr allelic distribution conformed to the Hardy-Weinberg equilibrium (X2= 0.161, P> 0.05). Observed allelic frequencies were 0.96 and 0.04 for wild-type T and mutant C alleles respectively. There was no significant relationship between AS3MT SNP, arsenic concentrations and schistosomiasis associated bladder pathology. In conclusion, the community is highly exposed to arsenic, although with a possible genetic advantage of increased AS3MT catalytic activity. However, we see the need for urgent intervention as inter-individual differences in arsenic metabolism may influence the bladder pathology status of individuals in the community. And although urogenital schistosomiasis is waning in Eggua, it is not known what synergy the infection and high arsenic exposure may wield on bladder pathology.


2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
G Di Martino ◽  
P Di Giovanni ◽  
P Scampoli ◽  
F Meo ◽  
F Cedrone ◽  
...  

Abstract Background Arsenic is a toxic metalloid element frequently found in the environment. Chronic arsenic exposure is a critical public health issue in many countries since the identification of arsenic and its compounds as human carcinogens by the World Health Organization. After absorption, inorganic arsenic (iAs) is mainly methylated into monomethylated and dimethylated compounds (MMA, DMA), which are then excreted through the kidney together with unmethylated iAs. Whether the methylation process is to detoxify or potentiate arsenic toxicity, however, remains an ongoing debate. The purpose of this systematic review was to conduct a comprehensive meta-analysis to estimate the association between arsenic exposure and urothelial cancer. Methods 10 observational studies met the inclusion criteria and were included in the systematic review. IAs%, MMA% and DMA% were extracted from each paper. Weighted Mean Differences with 95% confidence intervals were defined according to Cases minus Controls. Pooled risk estimates from individual studies were assessed using random effects models. Meta-regression analysis was performed to estimate the extent of urothelial cancer risk as a function of iAs%, MMA% and DMA%. Results Results showed as patients with urothelial cancer presented higher level of urinary iAs% (WMD 2.70, 95%CI 0.64-4.76), MMA% (WMD 2.81, 95%CI 1.43-4.20) and DMA% (WMD-3.44, 95%CI-6.57–0.30). Conclusions These findings suggest that higher level of iAs% and MMA% and lower level of DMA% were associated with an increased risk of urothelial cancer. Additional population based studies are needed to understand the role of arsenic in cancer development. Understanding the meaning of arsenic metabolism could improve the risk assessment of arsenic toxicity and provide a potential tool for disease prediction and prevention. Key messages Higher level of iAs%, MMA% and DMA% were associated with an increased risk of urothelial cancer. Understanding the meaning of arsenic metabolism could improve the risk assessment of arsenic toxicity.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Molly Scannell Bryan ◽  
Tamar Sofer ◽  
Majid Afshar ◽  
Yasmin Mossavar-Rahmani ◽  
H. Dean Hosgood ◽  
...  

AbstractArsenic exposure has been linked to poor pulmonary function, and inefficient arsenic metabolizers may be at increased risk. Dietary rice has recently been identified as a possible substantial route of exposure to arsenic, and it remains unknown whether it can provide a sufficient level of exposure to affect pulmonary function in inefficient metabolizers. Within 12,609 participants of HCHS/SOL, asthma diagnoses and spirometry-based measures of pulmonary function were assessed, and rice consumption was inferred from grain intake via a food frequency questionnaire. After stratifying by smoking history, the relationship between arsenic metabolism efficiency [percentages of inorganic arsenic (%iAs), monomethylarsenate (%MMA), and dimethylarsinate (%DMA) species in urine] and the measures of pulmonary function were estimated in a two-sample Mendelian randomization approach (genotype information from an Illumina HumanOmni2.5-8v1-1 array), focusing on participants with high inferred rice consumption. Among never-smoking high inferred consumers of rice (n = 1395), inefficient metabolism was associated with past asthma diagnosis and forced vital capacity below the lower limit of normal (LLN) (OR 1.40, p = 0.0212 and OR 1.42, p = 0.0072, respectively, for each percentage-point increase in %iAs; OR 1.26, p = 0.0240 and OR 1.24, p = 0.0193 for %MMA; OR 0.87, p = 0.0209 and OR 0.87, p = 0.0123 for the marker of efficient metabolism, %DMA). Among ever-smoking high inferred consumers of rice (n = 1127), inefficient metabolism was associated with peak expiratory flow below LLN (OR 1.54, p = 0.0108/percentage-point increase in %iAs, OR 1.37, p = 0.0097 for %MMA, and OR 0.83, p = 0.0093 for %DMA). Less efficient arsenic metabolism was associated with indicators of pulmonary dysfunction among those with high inferred rice consumption, suggesting that reductions in dietary arsenic could improve respiratory health.


2015 ◽  
Vol 114 (7) ◽  
pp. 1064-1071 ◽  
Author(s):  
Hui Ma ◽  
Huandong Lin ◽  
Yu Hu ◽  
Xiaoming Li ◽  
Wanyuan He ◽  
...  

Postmenopausal women are at increased risk of CVD: the increased serum ferritin level may be involved in the pathogenesis. The aim of the present study is to investigate the relationship of ferritin and carotid atherosclerosis in postmenopausal women. A total of 1178 postmenopausal women (mean age, 60·8 years) were enrolled from the Changfeng Study. A standard interview, anthropometric measurements and laboratory analyses were performed for each participant. Bilateral CIMT (carotid intima–media thickness) were measured using ultrasonography, and the presence of carotid plaques was assessed. Serum ferritin was measured using electrochemiluminescence immunoassay. The results showed that serum ferritin was 181·9 (sd 65·8) ng/ml in the postmenopausal women. Multivariate, linear, stepwise regression analysis demonstrated that age (standardised β = 0·233, P< 0·001), alanine transaminase (standardised β = 0·194, P< 0·001), log homeostasis model assessment index for insulin resistance (standardised β = 0·181, P< 0·001), TAG (standardised β = 0·083, P= 0·003), Hb (standardised β = 0·080, P= 0·004) and PPG (2-h glucose levels following a 75-g oral glucose challenge) (standardised β = 0·079, P= 0·004) were independently associated with serum ferritin. Compared with the ferritin level of subjects in the first quartile, that in the fourth quartile had greater CIMT, and higher prevalence of carotid plaque. After adjusting for conventional CVD risk factors, Hb, leucocytes, log urine albumin:creatinine ratio and liver function, the ferritin level of postmenopausal women in the fourth quartile had a 1·587-fold increased risk of carotid plaques relative to those in the lowest quartile. In conclusion, these results suggest that serum ferritin is independently and positively associated with carotid atherosclerosis in postmenopausal women and that ferritin may be implicated in atherosclerosis.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Binh An P Phan ◽  
Bernard Weigel ◽  
Yifei Ma ◽  
Rebecca Scherzer ◽  
Danny Li ◽  
...  

Background: While HIV infection is associated with increased risk of ASCVD (atherosclerotic cardiovascular disease), it is unknown whether guidelines can identify HIV-infected adults who may benefit from statins. The purpose of our study was to compare the 2013 ACC/AHA and 2004 ATP III recommendations in a HIV population, and to evaluate associations with carotid artery intima-media thickness (CIMT) and plaque. Methods: We used ultrasound to measure CIMT at baseline and 3 years later in 352 HIV-infected adults with no ASCVD and not on statins. Plaque was defined as IMT > 1.5 mm. We compared 2013 ACC/AHA and 2004 ATP III recommendations, and evaluated associations with CIMT and plaque. Results: At baseline, the median age was 43 (IQR 39-49), 85% were male, 74% were on antiretroviral medication, and 50% had plaque. At follow-up, the median IMT progression was 0.052 mm/yr, and 66% had plaque. The 2013 guideline was more likely to recommend statins compared with the 2004 guideline, both overall (26% vs. 14%, p<.001), in those with plaque (32% vs. 17%, p=.0002), and in those without plaque (16% vs. 7%, p=.025). In unadjusted linear regression, the 2004 and 2013 risk score were strongly associated with CIMT (0.01 mm per 10% increase in risk, p<.001) and with CIMT progression (0.01 mm/yr per 10% increase in risk, p<.001). In multivariate analysis, older age, higher LDL-C, pack-years of smoking, and history of opportunistic infection were associated with baseline plaque. Conclusions: While the 2013 ACC/AHA guideline recommended statins to a greater number of HIV-infected adults compared to the 2004 ATP III guideline, both failed to recommend therapy in the majority of HIV-affected adults with carotid plaque. Both the 2004 and 2013 guidelines predicted higher levels of baseline CIMT and faster progression. HIV-specific guidelines that include detection of subclinical atherosclerosis may help to identify HIV-infected adults who are at increased ASCVD risk and may benefit from statins.


2019 ◽  
Vol 16 (1) ◽  
pp. 39-45
Author(s):  
Cemal Kemaloglu ◽  
Melek Didem Kemaloglu

Objective: The aim of this study is to identify the relationship between carotid intima-media thickness (c-imt) and non-alcoholic fatty liver disease (NAFLD), and to determine whether NAFLD is an independent predictor for the progression of atherosclerosis.  Method: This is a prospective randomized controlled study. 103 NAFLD patients who have hepatosteatosis with grade II and above were enrolled in this study. Patients were divided into NAFLD with metabolic syndrome (MS) and NAFLD without MS groups and compared with 50 healthy people. Basal demographic characteristics and C-imt of all patients and control group were measured.  Results: C-imt and carotid cross sectional area rates in the NAFLD groups were significantly higher than those in the control group. The mean and max. c-imt levels were significantly higher in the NAFLD group with metabolic syndrome (p<0,001). Homeostatic Model of Assessment-Insulin Resistance (HOMA-IR) levels were increased in the group with metabolic syndrome than those in the group without metabolic syndrome, with statistical significance (p<0.001). There was no difference in c-imt levels between HOMA-IR positive and negative groups (p=0.254) in patients with NAFLD and without metabolic syndrome. There was only a mild positive corelation between c-imt levels and high sensitive C-Reactive protein (hs-CRP) levels in metabolic syndrome positive group (p=0.026 r=0.30).  Conclusion: NAFLD was a significant predictor to determine the increased risk of carotid atherosclerosis. 


Metallomics ◽  
2012 ◽  
Vol 4 (1) ◽  
pp. 91-100 ◽  
Author(s):  
Tetsuro Agusa ◽  
Takashi Kunito ◽  
Nguyen Minh Tue ◽  
Vi Thi Mai Lan ◽  
Junko Fujihara ◽  
...  

Diabetes Care ◽  
2015 ◽  
pp. dc141641 ◽  
Author(s):  
Chin-Chi Kuo ◽  
Barbara V. Howard ◽  
Jason G. Umans ◽  
Matthew O. Gribble ◽  
Lyle G. Best ◽  
...  

2016 ◽  
Vol 19 (1) ◽  
pp. 63-70 ◽  
Author(s):  
D Popović ◽  
J Nikolajević Starčević ◽  
M Šantl Letonja ◽  
J Makuc ◽  
A Cokan Vujkovac ◽  
...  

ABSTRACTThe platelet endothelial cell adhesion molecule 1 (PECAM-1) plays an important role in many inflammatory processes, including the development of atherosclerosis. Polymorphism rs668 of the PECAM-1 gene (373C/G) is functional, and it was reported to be associated with increased serum levels of PECAM-1. We investigated the association between the rs668 polymorphism of PECAM-1 and subclinical markers of carotid atherosclerosis in subjects with type 2 diabetes mellitus (T2DM). Five hundred and ninety-five T2DM subjects and 200 control subjects were enrolled. The carotid intima-media thickness (CIMT) and plaque characteristics (presence and structure) were assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. Geno-typing of the PECAM-1 gene polymorphism (rs668) was performed using KASPar assays. The control examinations were performed 3.8 ± 0.5 years after the initial examination. Higher CIMT was found in patients with T2DM in comparison with subjects without T2DM. Statistically sig-nificantly faster progression of the atherosclerotic markers was shown in subjects with T2DM in comparison with the control group. When adjusted to other risk factors, the rs668 GG genotype was associated with an increased risk of carotid plaques in subjects with T2DM. We concluded that our study demonstrated a minor effect of the rs668 PECAM-1 on markers of carotid atherosclerosis in subjects with T2DM.


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