Our study showed that total urinary arsenic concentrations were positively correlated with renal cell carcinoma (RCC). Chronic inflammation is a key player in the development of RCC. This study ...explored the association between nucleotide-binding domain-like receptor protein 3 (NLRP3) genotypes and the development of RCC. We also investigated whether any of the NLRP3 genotypes modified the risk between arsenic and RCC. We recruited 350 RCC patients and 700 age-sex matched controls. RCC was confirmed by pathological assessment following surgical resection or image-guided biopsy of a renal tumor. Fifteen sites of NLRP3 gene polymorphisms were identified using the Agena Bioscience MassARRAY platform. The concentrations of the urinary arsenic species were determined by HPLC-HG-AAS. There was a significant dose-dependent association between arsenic and RCC. In addition, six of thirteen NLRP3 alleles, including rs12239046 C, rs10925025 G, rs1539019 C, rs10925026 A, rs10157379 T, and rs12143966 A, had increased odds ratios (ORs) for RCC than other NLRP3 alleles. Among these sites, we found the novel haplotype of five tag-SNPs (C-A-A-A-A) was significantly related to RCC, the OR and 95% confidence interval was 1.44 (1.08-1.92). Furthermore, participants with high total urinary arsenic levels and the NLRP3 rs1539019 C allele had significantly multiplicative and additive interactions for the risk of RCC (p
= 0.012). This study is the first to identify the modified effects of NLRP3 risk alleles involved in the association between arsenic and RCC risk in a population with low arsenic exposure.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Adiponectin is an adipokine multipeptide hormone with insulin-sensitizing; anti-atherosclerotic; and anti-inflammatory properties. Chronic kidney disease (CKD) may be associated with low adiponectin. ...The adiponectin gene
is thought to be the only major gene responsible for plasma adiponectin levels; which are associated with diabetes and diabetic nephropathy. The purpose of this study was to investigate the association between
polymorphism and CKD. In addition; the combined effects of
polymorphism and diabetes and levels of total urinary arsenic and blood cadmium on CKD were also explored. This study included 215 CKD patients and 423 age-sex matched controls. The
polymorphisms were determined using the Agena Bioscience Mass ARRAY System. The levels of blood cadmium and urinary arsenic species were measured. The
rs182052 GA/AA genotype had a marginally lower odds ratio (OR) for CKD than the GG genotype. The OR (95% confidence interval; CI) was 16.33 (5.72-46.66) of CKD in subjects carrying the
rs182052 GG genotype and diabetes compared to non-diabetes subjects carrying the
rs182052 GA/AA genotype; the interaction term had
= 0.015; and the synergy index was 6.64 (1.81-24.36) after multivariate adjustment. A significant interaction of diabetes and
rs1501299 risk genotype increased the OR of CKD after multivariate adjustment with a synergy index of 0.31 (0.11-0.86) and a multiplicative interaction with
= 0.001. These results suggest that
rs182052 and rs1501299 risk genotypes may significantly modify the association between diabetes and CKD but not the association between total urinary arsenic and blood cadmium and CKD.
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•Plasma selenium level was significantly positively associated with eGFR in a dose-dependent manner.•High plasma selenium and low red blood cell cadmium or lead levels significantly interacted to ...decrease the OR for CKD.•High plasma selenium and low red blood cell lead levels significantly interacted to increase the eGFR.
This study aimed to determine the interaction of red blood cell cadmium and lead, total urinary arsenic, and plasma selenium in chronic kidney disease (CKD). We recruited 220 CKD patients as well as 438 gender- and age-matched controls, and we defined CKD as <60 mL/min/1.73 m2 estimated glomerular filtration rate (eGFR) for three or more consecutive months. Plasma selenium and red blood cell cadmium and lead concentrations were measured by ICP-MS. Urinary arsenic species were determined via HPLC-HG-AAS and were summed to determine the total urinary arsenic concentration. Plasma selenium was positively correlated to eGFR, and subjects with high plasma selenium levels (>243.90 μg/L) had a significantly lower odds ratio (OR) and 95% confidence interval (CI) (0.23, 0.13–0.42) for CKD compared to those with low plasma selenium levels (≤ 196.70 μg/L). High plasma selenium and low red blood cell cadmium or lead concentrations interacted to decrease the OR and 95% CI for CKD (0.12, 0.06–0.26; 0.09, 0.04–0.19). High plasma selenium and low red blood cell lead levels also interacted to increase the eGFR (20.70, 15.56–26.01 mL/min/1.73 m2). This study is the first to suggest that selenium modifies the eGFR and OR in CKD induced by environmental toxicants.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The tissue inhibitor of metalloproteinase 3 (TIMP3) is known to be an anti-fibrotic factor. Arsenic, lead, and cadmium exposure and selenium intake may affect TIMP3 expression. The downregulation of ...TIMP3 expression is related to kidney fibrosis. Genotypes of TIMP3 are related to hypertension and cardiovascular diseases. Therefore, this study explored whether TIMP3 polymorphism is associated with hypertension-related chronic kidney disease (CKD). In addition, the combined effects of TIMP3 polymorphism and total urinary arsenic, blood lead and cadmium, and plasma selenium concentrations on CKD, were investigated. This was a case-control study, with 213 CKD patients and 423 age- and sex-matched controls recruited. Polymerase chain reaction-restriction fragment length polymorphism was used to determine TIMP3 gene polymorphisms. The concentrations of urinary arsenic species, plasma selenium, and blood lead and cadmium were measured. The odds ratio (OR) of CKD in the TIMP3rs9609643 GA/AA genotype was higher than that of the GG genotype at high levels of total urinary arsenic and blood lead; the OR and 95% confidence interval (CI) were 0.57 (0.31-1.05) and 0.52 (0.30-0.93), respectively, after multivariate adjustment. High blood lead levels tended to interact with the TIMP3rs9609643 GG genotype to increase the OR of CKD, and gave the highest OR (95% CI) for CKD of 5.97 (2.60-13.67). Our study supports a possible role for the TIMP3rs9609643 risk genotype combined with high total urinary arsenic or with high blood lead concentration to increase the OR of CKD.
Chronic inflammation is the cause of chronic kidney disease (CKD). The nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome plays a vital role in the inflammation process and is ...associated with the regulatory effects of NLRP3 gene polymorphisms. This study evaluated the association between NLRP3 gene polymorphisms and CKD, and further explored whether the association of environmental metals with CKD varied by the NLRP3 genotypes. A total of 218 CKD patients and 427 age- and sex-matched healthy controls were recruited in this clinic-based case-control study. Patients were identified as having CKD if their estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m
and stage 3-5 for at least 3 months. We examined the genotypes of fifteen common ssingle-nucleotide polymorphisms in NLRP3 genes. Concentrations of total urinary arsenic were examined by summing of urinary inorganic arsenic species. Concentrations of selenium, cadmium, and lead were measured from blood samples. Associations between NLRP3 polymorphisms, environmental metals exposure, and CKD were evaluated using multivariable logistic regression while controlling for confounders. We observed that the odds of carrying NLRP3 rs4925650 GA/AA genotypes, NLRP3 rs1539019 CA/AA genotypes, and NLRP3 rs10157379 CT/TT genotypes were significantly higher among CKD cases compared to controls, with the adjusted odds ratio (95% confidence interval) were 1.54 (1.01-2.36), 1.56 (1.04-2.33), and 1.59 (1.05-2.38), respectively. The significant multiplicative interactions were identified between high levels of blood lead and NLRP3 rs4925650 GA/AA genotypes; high levels of blood cadmium or low levels of plasma selenium and the NLRP3 haplotype (rs4925648, rs4925650, rs12048215, and rs10754555) C-A-A-C multiplicatively interacted to increase the risk of CKD. Our results imply that NLRP3 polymorphisms may play an important role in the development of environmental metals exposure related CKD.
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This study investigated whether plasma selenium levels modified the risk for prostate cancer (PC) related to arsenic exposure. We conducted a case-control study that included 318 PC patients and 318 ...age-matched, healthy control subjects. Urinary arsenic profiles were examined using HPLC-HG-AAS and plasma selenium levels were measured by ICP-MS. We found that plasma selenium levels displayed a significant dose-dependent inverse association with PC. The odds ratio (OR) and 95% confidence interval (CI) for PC was 0.07 (0.04–0.13) among participants with a plasma selenium level >28.06 μg/dL vs. ≤19.13 μg/dL. A multivariate analysis showed that participants with a urinary total arsenic concentration >29.28 μg/L had a significantly higher OR (1.75, 1.06–2.89) for PC than participants with ≤29.89 μg/L. The combined presence of a low plasma selenium level and a high urinary total arsenic concentration exponentially increased the OR for PC, and additively interacted with PSA at levels ≥20 ng/mL. This is the first epidemiological study to examine the combined effects of plasma selenium and urinary total arsenic levels on the OR for PC. Our data suggest a low plasma selenium level coupled with a high urinary total arsenic concentration creates a significant risk for aggressive PC.
•Plasma Se was significantly inversely associated with PC in a dose-response manner.•Low plasma Se levels interact with high urinary total As levels to increase the risk for PC.•Low plasma Se levels interact with high urinary total As levels to increase the risk for a PSA ≥ 20 in patients with PC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background Inorganic arsenic has been linked to decreased kidney function through oxidative damage. Arsenic methylation is believed to be a pathway for arsenic metabolism. Lycopene is an antioxidant ...that reduces oxidative stress; however, the association between urinary arsenic species, plasma lycopene level, and chronic kidney disease (CKD) has seldom been evaluated. Study Design Case-control study. Setting & Participants 125 patients with CKD and 229 controls were recruited from a hospital-based pool. Predictor Urinary arsenic species and plasma lycopene level. Outcomes & Measurements CKD was defined as estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 , calculated by using the Modification of Diet in Renal Disease Study equation. Plasma lycopene was measured by means of high-performance liquid chromatography. Urinary arsenic species, including arsenite, arsenate, monomethylarsonic acid, and dimethylarsinic acid, were determined by means of high-performance liquid chromatography and hydride generator–atomic absorption spectrometry. Results Lycopene level was associated positively with eGFR, and participants with a high serum lycopene level had a significant, inverse association with CKD (odds ratio, 0.41; 95% confidence interval, 0.21 to 0.81). Total arsenic level was associated significantly with CKD in a dose-response relationship, especially in participants with a total arsenic level greater than 20.74 compared with 11.78 μg/g creatinine or less (odds ratio, 4.34; 95% confidence interval, 1.94 to 9.69). Furthermore, participants with a high urinary total arsenic level or participants with a low percentage of dimethylarsinic acid had a positive association with CKD when their plasma lycopene level was low. Limitations Because of the single spot evaluation of plasma antioxidants and urinary arsenic species and the small sample size, statistical significance should be interpreted with caution. Conclusions This study shows that high urinary total arsenic or low plasma lycopene level is associated positively with CKD. Results suggest that the capacity for arsenic methylation may be associated with CKD in individuals who ingest low arsenic levels in drinking water and also have a low plasma lycopene level.
This study hypothesized that plasma folate and vitamin B12 levels modified the association between blood lead and cadmium and total urinary arsenic levels and bone loss. A total of 447 study subjects ...who received a physical examination at the Wanfang Hospital Medical Center were recruited. Bone loss was defined as a calcaneus bone mineral density T-score less than −1. Blood cadmium and lead concentrations were measured by ICP-MS. Urinary arsenic species were determined using HPLC-HG-AAS. A SimulTRAC-SNB radioassay was used to measure plasma folate, vitamin B12, and homocysteine levels. Total urinary arsenic and blood lead concentration were positively correlated with the odds ratio (OR) for bone loss in a dose–response manner. The OR and 95% confidence interval (CI) for bone loss in participants with blood lead concentrations > 56.14 versus ≤33.82 μg/dL were 1.82 and 1.10–3.01. No correlation between plasma folate and vitamin B12 levels alone and bone loss was observed. However, this study is the first observational study to find that blood lead concentrations tend to increase the OR of bone loss in a low plasma folate and plasma vitamin B12 group with multivariate ORs (95% CI) of 2.44 (0.85–6.96).
Long interspersed nuclear element-1 (LINE-1) methylation serves as an indicator of global DNA methylation. This study explored the correlation between LINE-1 methylation and chronic kidney disease ...(CKD). We also evaluated whether LINE-1 methylation could modify the association between CKD and metal exposure. A total of 213 patients with clinically defined CKD, without hemodialysis and 416 age and sex matched controls were recruited. Levels of LINE-1 methylation, total urinary arsenic, blood lead, blood cadmium, and plasma selenium were assessed. The results reveal a positive association between LINE-1 methylation and CKD, with an odds ratio (OR) of 5.30 (95% confidence interval: 2.81 to 9.99). Total urinary arsenic and blood cadmium concentrations were positively related with LINE-1 methylation. This study was the first to observe that low plasma selenium, high blood cadmium, and high blood lead levels significantly and additively interact with increased LINE-1 methylation to increase the OR of CKD. Additionally, high LINE-1 methylation interacted multiplicatively with low plasma selenium to increase the OR of CKD (p < 0.001). This study highlighted the significant association between LINE-1 hypermethylation and CKD. Furthermore, the results demonstrate that LINE-1 methylation can interact with high blood cadmium or low plasma selenium to affect CKD risk.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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