| 1. |
- Kuehnelt, Doris, et al.
(författare)
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Selenium metabolism to the trimethylselenonium ion (TMSe) varies markedly because of polymorphisms in the indolethylamine N-methyltransferase gene
- 2015
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 102:6, s. 1406-1415
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Tidskriftsartikel (refereegranskat)abstract
- Background: Selenium is an essential element, but its metabolism in humans is not well characterized. A few small studies indicate that the trimethylselenonium ion (TMSe) is a common selenium metabolite in humans. Objective: This study aimed to elucidate the human metabolism of selenium to TMSe. Design: Study individuals constituted subsamples of 2 cohorts: 1) pregnant women (n = 228) and their 5-y-old children (n = 205) in rural Bangladesh with poor selenium status [median urinary selenium (U-Se): 6.4 mu g/L in mothers, 14 mu g/L in children] and 2) women in the Argentinian Andes (n = 83) with adequate selenium status (median U-Se: 24 mu g/L). Total U-Se and blood selenium were measured by inductively coupled plasma mass spectrometry (ICPMS), and urinary concentrations of TMSe were measured by high-performance liquid chromatography/vapor generation/ICPMS. A genomewide association study (GWAS) was performed for 1,629,299 (after filtration) single nucleotide polymorphisms (SNPs) in the Bangladeshi women (n = 72) by using Illumina Omni5M, and results were validated by using real-time polymerase chain reaction. Results: TMSe "producers" were prevalent (approximately one-third) among the Bangladeshi women and their children, in whom TMSe constituted similar to 10-70% of U-Se, whereas "nonproducers" had, on average, 0.59% TMSe. The TMSe-producing women had, on average, 2-mu g U-Se/L higher concentrations than did the nonproducers. In contrast, only 3 of the 83 Andean women were TMSe producers (6-15% TMSe in the urine); the average percentage among the nonproducers was 0.35%. Comparison of the percentage of urinary TMSe in mothers and children indicated a strong genetic influence. The GWAS identified 3 SNPs in the indolethylamine N-methyltransferase gene (INMT) that were strongly associated with percentage of TMSe (P < 0.001, false-discovery rate corrected) in both cohorts. Conclusions: There are remarkable population and individual variations in the formation of TMSe, which could largely be explained by SNPs in INMT. The TMSe-producing women had higher U-Se concentrations than did nonproducers, but further elucidation of the metabolic pathways of selenium is essential for the understanding of its role in human health.
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| 2. |
- Engström, Karin, et al.
(författare)
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Evaluation of the impact of genetic polymorphisms in glutathione-related genes on the association between methylmercury or n-3 polyunsaturated long chain fatty acids and risk of myocardial infarction : a case-control study
- 2011
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Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 10:33
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Tidskriftsartikel (refereegranskat)abstract
- Background: The n-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, which are present in fish, are protective against myocardial infarction. However, fish also contains methylmercury, which influences the risk of myocardial infarction, possibly by generating oxidative stress. Methylmercury is metabolized by conjugation to glutathione, which facilitates elimination. Glutathione is also an antioxidant. Individuals with certain polymorphisms in glutathione-related genes may tolerate higher exposures to methylmercury, due to faster metabolism and elimination and/or better glutathione-associated antioxidative capacity. They would thus benefit more from the protective agents in fish, such as eicosapentaenoic+docosahexaenoic acid and selenium. The objective for this study was to elucidate whether genetic polymorphisms in glutathione-related genes modify the association between eicosapentaenoic+docosahexaenoic acid or methylmercury and risk of first ever myocardial infarction. Methods: Polymorphisms in glutathione-synthesizing (glutamyl-cysteine ligase catalytic subunit, GCLC and glutamyl-cysteine ligase modifier subunit, GCLM) or glutathione-conjugating (glutathione S-transferase P, GSTP1) genes were genotyped in 1027 individuals from northern Sweden (458 cases of first-ever myocardial infarction and 569 matched controls). The impact of these polymorphisms on the association between erythrocyte-mercury (proxy for methylmercury) and risk of myocardial infarction, as well as between plasma eicosapentaenoic+docosahexaenoic acid and risk of myocardial infarction, was evaluated by conditional logistic regression. The effect of erythrocyte-selenium on risk of myocardial infarction was also taken into consideration. Results: There were no strong genetic modifying effects on the association between plasma eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury and risk of myocardial infarction risk. When eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury were divided into tertiles, individuals with GCLM-588 TT genotype displayed a lower risk relative to the CC genotype in all but one tertile; in most tertiles the odds ratio was around 0.5 for TT. However, there were few TT carriers and the results were not statistically significant. The results were similar when taking plasma eicosapentaenoic+docosahexaenoic acid, erythrocyte-selenium and erythrocyte-mercury into account simultaneously. Conclusions: No statistically significant genetic modifying effects were seen for the association between plasma eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury and risk of myocardial infarction. Still, our results indicate that the relatively rare GCLM-588 TT genotype may have an impact, but a larger study is necessary for confirmation.
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| 3. |
- Albin, Maria, et al.
(författare)
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0253 Hairdressers are occupationally exposed to ortho- and meta- toluidine
- 2014
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 71 Suppl 1, s. 32-33
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Konferensbidrag (refereegranskat)abstract
- Hairdressing work is classified as carcinogenic based on excess risk for bladder cancer. We aimed at evaluating if current hairdressers are exposed to established/suspected bladder carcinogens (aromatic amines) and indicate possible sources of exposure.
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| 8. |
- Broberg Palmgren, Karin, et al.
(författare)
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Influence of genetic factors on toluene diisocyanate-related symptoms: evidence from a cross-sectional study
- 2008
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Ingår i: Environmental Health. - 1476-069X. ; 7:15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Toluene diisocyanate (TDI) is a highly reactive compound used in the production of, e. g., polyurethane foams and paints. TDI is known to cause respiratory symptoms and diseases. Because TDI causes symptoms in only a fraction of exposed workers, genetic factors may play a key role in disease susceptibility. Methods: Workers (N = 132) exposed to TDI and a non-exposed group ( N = 114) were analyzed for genotype (metabolising genes: CYP1A1*2A, CYP1A1*2B, GSTM1*O, GSTM3*B, GSTP1 1105V, GSTP1 A114V, GSTT1*O, MPO -463, NAT1*3, *4, *10, *11, *14, *15, NAT2*5, *6, *7, SULT1A1 R213H; immune-related genes: CCL5 -403, HLA-DQB1* 05, TNF-308, TNF-863) and symptoms of the eyes, upper and lower airways ( based on structured interviews). Results: For three polymorphisms: CYP1A1*2A, CYP1A1*2B, and TNF -308 there was a pattern consistent with interaction between genotype and TDI exposure status for the majority of symptoms investigated, although it did reach statistical significance only for some symptoms: among TDI-exposed workers, the CYP1A1 variant carriers had increased risk (CYP1A1*2A and eye symptoms: variant carriers OR 2.0 95% CI 0.68-6.1, p-value for interaction 0.048; CYP1A1*2B and wheeze: IV carriers OR = 12, 1.4-110, p-value for interaction 0.057). TDI-exposed individuals with TNF-308 A were protected against the majority of symptoms, but it did not reach statistical significance. In the non-exposed group, however, TNF -308 A carriers showed higher risk of the majority of symptoms ( eye symptoms: variant carriers OR = 2.8, 1.1-7.1, p-value for interaction 0.12; dry cough OR = 2.2, 0.69-7.2, p-value for interaction 0.036). Individuals with SULT1A1 213H had reduced risk both in the exposed and non-exposed groups. Other polymorphisms, showed associations to certain symptoms: among TDI-exposed, NAT1*10 carriers had a higher risk of eye symptoms and CCL5 -403 AG+AA as well as HLA-DQB1 *05 carriers displayed increased risk of symptoms of the lower airways. GSTM1, GSTM3 and GSTP1 only displayed effects on symptoms of the lower airways in the non-exposed group. Conclusion: Specific gene-TDI interactions for symptoms of the eyes and lower airways appear to exist. The results suggest different mechanisms for TDI- and non- TDI-related symptoms of the eyes and lower airways.
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| 9. |
- Broberg Palmgren, Karin, et al.
(författare)
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Lithium in Drinking Water and Thyroid Function
- 2011
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 119:6, s. 827-830
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: High concentrations of lithium in drinking water were previously discovered in the Argentinean Andes Mountains. Lithium is used worldwide for treatment of bipolar disorder and treatment-resistant depression. One known side effect is altered thyroid function. OBJECTIVES: We assessed associations between exposure to lithium from drinking water and other environmental sources and thyroid function. METHODS: Women (n = 202) were recruited in four Andean villages in northern Argentina. Lithium exposure was assessed based on concentrations in spot urine samples, measured by inductively coupled plasma mass spectrometry. Thyroid function was evaluated by plasma free thyroxine (T-4) and pituitary gland thyroid-stimulating hormone (TSH), analyzed by routine immuno metric methods. RESULTS: The median urinary lithium concentration was 3,910 mu g/L (5th, 95th percentiles, 270 mu g/L, 10,400 mu g/L). Median plasma concentrations (5th, 95th percentiles) of T-4 and TSH were 17 pmol/L (13 pmol/L, 21 pmol/L) and 1.9 mIU/L, (0.68 mIU/L, 4.9 mIU/L), respectively. Urine lithium was inversely associated with T-4 [beta for a 1,000-mu g/L increase = -0.19; 95% confidence interval (CI), -0.31 to -0.068; p = 0.002] and positively associated with TSH (beta = 0.096; 95% CI, 0.033 to 0.16; p = 0.003). Both associations persisted after adjustment (for T-4, beta = -0.17; 95% CI, -0.32 to -0.015; p = 0.032; for TSH: beta = 0.089; 95% CI, 0.024 to 0.15; p = 0.007). Urine selenium was positively associated with T-4 (adjusted T-4 for a 1 mu g/L increase: beta = 0.041; 95% CI, 0.012 to 0.071; p = 0.006). CONCLUSIONS: Exposure to lithium via drinking water and other environmental sources may affect thyroid function, consistent with known side effects of medical treatment with lithium. This stresses the need to screen for lithium in all drinking water sources.
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| 10. |
- Concha, Gabriela, et al.
(författare)
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High-Level Exposure to Lithium, Boron, Cesium, and Arsenic via Drinking Water in the Andes of Northern Argentina.
- 2010
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Ingår i: Environmental Science & Technology. - : American Chemical Society (ACS). - 1520-5851 .- 0013-936X. ; 44:17, s. 6875-6880
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Tidskriftsartikel (refereegranskat)abstract
- Elevated concentrations of arsenic in drinking water are common worldwide, however, little is known about the presence of other potentially toxic elements. We analyzed 31 different elements in drinking water collected in San Antonio de los Cobres and five surrounding Andean villages in Argentina, and in urine of the inhabitants, using ICP-MS. Besides confirmation of elevated arsenic concentrations in the drinking water (up to 210 mug/L), we found remarkably high concentrations of lithium (highest 1000 mug/L), cesium (320 mug/L), rubidium (47 mug/L), and boron (5950 mug/L). Similarly elevated concentrations of arsenic, lithium, cesium, and boron were found in urine of the studied women (N = 198): village median values ranged from 26 to 266 mug/L of arsenic, 340 to 4550 mug/L of lithium, 34 to 531 mug/L of cesium, and 2980 to 16 560 mug/L of boron. There is an apparent risk of toxic effects of long-term exposure to several of the elements, and studies on associations with adverse human health effects are warranted, particularly considering the combined, life-long exposure. Because of the observed wide range of concentrations, all water sources used for drinking water should be screened for a large number of elements; obviously, this applies to all drinking water sources globally.
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