| 1. |
- Engström, Karin, et al.
(författare)
-
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
-
Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 10:33
-
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.
|
|
| 2. |
- Hrubá, Františka, et al.
(författare)
-
A regional comparison of children's blood cadmium, lead, and mercury in rural, urban and industrial areas of six European countries, and China, Ecuador, and Morocco
- 2023
-
Ingår i: International Journal of Occupational Medicine and Environmental Health. - Poland : Nofer Institute of Occupational Medicine. - 1232-1087 .- 1896-494X .- 2008-6520. ; 36:3, s. 349-364
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The authors aimed to evaluate whether blood cadmium (B-Cd), lead (B-Pb) and mercury (B-Hg) in children differ regionally in 9 countries, and to identify factors correlating with exposure.MATERIAL AND METHODS: The authors performed a cross-sectional study of children aged 7-14 years, living in 2007-2008 in urban, rural, or potentially polluted ("hot spot") areas (ca. 50 children from each area, in total 1363 children) in 6 European and 3 non-European countries. The authors analyzed Cd, Pb, and total Hg in blood and collected information on potential determinants of exposure through questionnaires. Regional differences in exposure levels were assessed within each country.RESULTS: Children living near industrial "hot-spots" had B-Cd 1.6 (95% CI: 1.4-1.9) times higher in the Czech Republic and 2.1 (95% CI:1.6-2.8) times higher in Poland, as compared to urban children in the same countries (geometric means [GM]: 0.13 μg/l and 0.15 μg/l, respectively). Correspondingly, B-Pb in the "hot spot" areas was 1.8 (95% CI: 1.6-2.1) times higher than in urban areas in Slovakia and 2.3 (95% CI: 1.9-2.7) times higher in Poland (urban GM: 19.4 μg/l and 16.3 μg/l, respectively). In China and Morocco, rural children had significantly lower B-Pb than urban ones (urban GM: 64 μg/l and 71 μg/l, respectively), suggesting urban exposure from leaded petrol, water pipes and/or coal-burning. Hg "hot spot" areas in China had B-Hg 3.1 (95% CI: 2.7-3.5) times higher, and Ecuador 1.5 (95% CI: 1.2-1.9) times higher, as compared to urban areas (urban GM: 2.45 μg/l and 3.23 μg/l, respectively). Besides industrial exposure, traffic correlated with B-Cd; male sex, environmental tobacco smoke, and offal consumption with B-Pb; and fish consumption and amalgam fillings with B-Hg. However, these correlations could only marginally explain regional differences.CONCLUSIONS: These mainly European results indicate that some children experience about doubled exposures to toxic elements just because of where they live. These exposures are unsafe, identifiable, and preventable and therefore call for preventive actions.
|
|
| 3. |
- Hruba, Frantiska, et al.
(författare)
-
Blood cadmium, mercury, and lead in children : An international comparison of cities in six European countries, and China, Ecuador, and Morocco
- 2012
-
Ingår i: Environment International. - Oxford : Elsevier. - 0160-4120 .- 1873-6750. ; 41, s. 29-34
-
Tidskriftsartikel (refereegranskat)abstract
- Children's blood-lead concentration (B-Pb) is well studied, but little is known about cadmium (B-Cd) and mercury (B-Hg), in particular for central Europe. Such information is necessary for risk assessment and management. Therefore, we here describe and compare B-Pb, B-Cd and B-Hg in children in six European, and three non-European cities, and identify determinants of these exposures. About 50 school children (7-14 years) from each city were recruited (totally 433) in 2007-2008. Interview and questionnaire data were obtained. A blood sample was analyzed: only two laboratories with strict quality control were used. The European cities showed only minor differences for B-Cd (geometric means 0.11-0.17 mu g/L) and B-Pb (14-20 mu g/L), but larger for B-Hg (0.12-0.94 mu g/L). Corresponding means for the non-European countries were 0.21-0.26, 32-71, and 0.3-3.2 mu g/L, respectively. For B-Cd in European samples, traffic intensity close to home was a statistically significant determinant, for B-Hg fish consumption and amalgam fillings, and for B-Pb sex (boys higher). This study shows that European city children's B-Cd and B-Pb vary only little between countries; B-Hg differs considerably, due to varying tooth restoration practices and fish intake. Traffic intensity seemed to be a determinant for B-Cd. The metal concentrations were low from a risk perspective but the chosen non-European cities showed higher concentrations than the cities in Europe. (C) 2011 Elsevier Ltd. All rights reserved.
|
|
| 4. |
- Lei, Lijian, et al.
(författare)
-
A polymorphism in metallothionein 1A (MT1A) is associated with cadmium-related excretion of urinary beta 2-microglobulin
- 2012
-
Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 1096-0333 .- 0041-008X. ; 265:3, s. 373-379
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Cadmium (Cd) toxicity of the kidney varies between individuals despite similar exposure levels. In humans Cd is mainly bound to metallothioneins (MT), which scavenge its toxic effects. Here we analyzed whether polymorphisms in MT genes MTIA and MT2A influence Cd-related kidney damage. Methods: In a cross-sectional study N = 512 volunteers were selected from three areas in South-Eastern China, which to varying degree were Cd-polluted from a smelter (control area [median Cd in urine U-Cd = 2.67 mu g/L], moderately [U-Cd = 423 mu g/L] and highly [U-Cd = 9.13 mu g/L] polluted areas). U-Cd and blood Cd (B-Cd) concentrations were measured by graphite-furnace atomic absorption spectrometry. MTIA rs11076161 (G/A), M72A rs10636 (G/C) and M72A rs28366003 (A/G) were determined by Taqman assays; urinary N-Acetyl-beta-(D)-Glucosaminidase (UNAG) by spectrometry, and urinary beta 2-microglobulin (UB2M) by ELISA. Results: Higher B-Cd (natural log-transformed) with increasing number of MTIA rs11076161 A-alleles was found in the highly polluted group (p-value trend = 0.033; all p-values adjusted for age, sex, and smoking). In a linear model a significant interaction between rs11076161 genotype and B-Cd was found for UNAG (p = 0.001) and UB2M concentrations (p = 0.001). Carriers of the rs11076161 AA genotype showed steeper slopes for the associations between Cd in blood and natural log-transformed UB2M (beta = 12, 95% CI 0.72-1.6) compared to GG carriers (beta = 030, 95% CI 0.15-0.45). Also for UNAG (natural log-transformed) carriers of the AA genotype had steeper slopes (beta = 0.55, 95% CI 027-0.84) compared to GG carriers (beta = 0.018, 95% CI - 0.79-0.11). Conclusions: MT1A rs11076161 was associated with B-Cd concentrations and Cd-induced kidney toxicity at high exposure levels. (C) 2012 Elsevier Inc. All rights reserved.
|
|
| 5. |
|
|
| 6. |
- Pawlas, Natalia, et al.
(författare)
-
Cadmium, mercury and lead in the blood of urban women in Croatia, the Czech Republic, Poland, Slovakia, Slovenia, Sweden, China, Ecuador and Morocco
- 2013
-
Ingår i: International Journal of Occupational Medicine and Environmental Health. - 1896-494X .- 1232-1087. ; 26:1, s. 58-72
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to make an international comparison of blood levels of cadmium (B-Cd), lead (B-Pb) and mercury (B-Hg) of women in seven European, and three non-European cities, and to identify determinants. About 50 women (age: 46-62) from each city were recruited (totally 480) in 2006-2009. Interview and questionnaire data were obtained. Blood samples were analysed in one laboratory to avoid interlaboratory variation. Between the European cities, the B-Pb and B-Cd results vary little (range of geometric means: 13.5-27.0 mu g/l and 0.25-0.65 mu g/l, respectively); the variation of B-Hg was larger (0.40-1.38 mu g/l). Between the non-European cities the results for B-Pb, B-Cd and B-Hg were 19.2-68.0, 0.39-0.99 and 1.01-2.73 mu g/l, respectively. Smoking was a statistically significant determinant for B-Cd, while fish and shellfish intakes contributed to B-Hg and B-Pb, amalgam fillings also contributed to B-Hg. The present results confirm the previous results from children; the exposure to lead and cadmium varies only little between different European cities suggesting that other factors than the living area are more important. The study also confirms the previous findings of higher cadmium and lead levels in some non-European cities. The geographical variation for mercury is significant.
|
|
| 7. |
- Rentschler, Gerda, et al.
(författare)
-
ATP13A2 (PARK9) polymorphisms influence the neurotoxic effects of manganese.
- 2012
-
Ingår i: NeuroToxicology. - : Elsevier BV. - 1872-9711 .- 0161-813X. ; 33:4, s. 697-702
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: A higher prevalence of individuals affected by Parkinsonism was found in Valcamonica, Italy. This may be related to ferro-alloy smelters in the area, releasing manganese (Mn) in the air, soil and water for about a century. There exists individual susceptibility for Mn neurotoxicity. AIM: To analyse how polymorphism in genes regulating Mn metabolism and toxicity can modify neurophysiological effects of Mn exposure. MATERIALS AND METHODS: Elderly (N=255) and adolescents (N=311) from Northern Italy were examined for neuromotor and olfactory functions. Exposure to Mn was assessed in blood and urine by atomic absorption spectroscopy and in soil by a portable instrument based on X-Ray fluorescence technology. Polymorphisms in the Parkinson-related gene ATPase type 13A2 (ATP13A2, also called PARK9: rs3738815, rs2076602, rs4920608, rs2871776 and rs2076600), and in the secretory pathway Ca(2+)/Mn(2+) ATPase isoform 1 gene (SPCA1: rs218498, rs3773814 and rs2669858) were analysed by TaqMan probes. RESULTS: For both adolescents and elderly, negative correlations between Mn in soil and motor coordination (R(s)=-0.20, p<0.001; R(s)=-0.13, p=0.05, respectively) were demonstrated. Also among adolescents, negative correlations were seen between Mn in soil with odor identification (R(s)=-0.17, p<0.01). No associations were seen for Mn in blood or urine. ATP13A2 polymorphisms rs4920608 and rs2871776 significantly modified the effects of Mn exposure on impaired motor coordination in elderly (p for interaction=0.029, p=0.041, respectively), also after adjustments for age and gender. The rs2871776 altered a binding site for transcription factor insulinoma-associated 1. CONCLUSIONS: ATP13A2 variation may be a risk marker for neurotoxic effects of Mn in humans.
|
|
| 8. |
- Rentschler, Gerda, et al.
(författare)
-
Cadmium concentrations in human blood and urine are associated with polymorphisms in zinc transporter genes.
- 2014
-
Ingår i: Metallomics. - : Oxford University Press (OUP). - 1756-5901 .- 1756-591X.
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Variation in susceptibility to cadmium (Cd) toxicity may partly be due to differences in Cd toxicokinetics. Experimental studies indicate that zinc (Zn) homeostasis proteins transport Cd. Objective. To evaluate the potential effect of variation in Zn-transporter genes (SLC39A8 and SLC39A14) on Cd concentrations in blood and urine. Methods. We studied women from the Argentinean Andes [median urinary Cd concentration (U-Cd) = 0.24 μg L(-1); erythrocyte Cd (Ery-Cd) = 0.75 μg L(-1) (n = 172)] and from rural Bangladesh [U-Cd = 0.54 μg L(-1) (n = 359), Ery-Cd = 1.1 μg L(-1) (n = 400)]. Polymorphisms (n = 36) were genotyped with Sequenom. Gene expression was measured in whole blood with Illumina DirectHyb HumanHT-12 v4.0. Results. Polymorphisms in SLC39A8 and SLC39A14 were associated with Ery-Cd concentrations in the Andean population. For SLC39A14, women carrying GT or TT genotypes of rs4872479 had 1.25 [95% confidence interval (CI) = 1.07-1.46] times higher Ery-Cd than women carrying GG. Also, women carrying AG or AA of rs870215 had 1.17 (CI 1.01-1.32) times higher Ery-Cd than those carrying GG. For SLC39A8, women carrying AG or GG of rs10014145 had 1.18 (CI 1.03-1.35) times higher Ery-Cd than those with AA, and carriers of CA or AA of rs233804 showed 1.22 (CI 1.04-1.42) times higher Ery-Cd than CC. The Bangladeshi population had similar, but statistically non-significant associations between some of these SNPs and Ery-Cd. In the Andean population, the genotypes of SLC39A14 rs4872479 and rs870215 associated with lower Ery-Cd showed positive correlations with plasma-Zn (P-Zn) and SLC39A14 expression. Conclusions. Polymorphisms in SLC39A14 and SLC39A8 seemed to affect blood Cd concentrations, for SLC39A14 this effect may occur via differential gene expression.
|
|
| 9. |
- Rentschler, Gerda
(författare)
-
Genetic variability and cadmium metabolism and toxicity
- 2014
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abstract: Cadmium (Cd) is ubiquitous in the environment. Human exposure in non-smokers occurs mainly via intake of healthy food like vegetables, cereals, and shellfish. Adverse health effects on kidney and bone at low-level environmental Cd exposure are well-documented in adults. There is considerable inter-individual variation in both metabolism (toxicokinetics) and toxicity (toxicodynamics) of Cd. This may be due to genetic factors. The aim of this thesis was to identify genetic factors that are associated with Cd metabolism and toxicity. As Cd is a foreign element, there is no endogenous metabolism of uptake. However, there is evidence that the transporters of other elements such as iron and zinc are not sufficiently specific to prevent uptake of Cd. Further, the zinc-binding protein metallothionein (MT) protects against toxicity of Cd in the kidney. Thus, the first study examined the association of single nucleotide polymorphisms (SNPs) in iron homeostasis genes with Cd concentrations in two groups of women, one from the Argentinean Andes and the other from rural Bangladesh. The second study examined the association of SNPs in two zinc homeostasis genes, SLC39A8 and SLC39A14 with Cd concentrations in the same groups of women as in the first study. The third study analysed whether polymorphisms in the metallothionein genes MT1A and MT2A influence Cd-related kidney damage in volunteers from three areas in southern China with various degrees of Cd pollution. All study designs were cross-sectional. We found (1) that one SNP in the iron-related transferrin receptor gene TFRC (rs3804141) was associated with Cd concentrations in urine in both women from Argentina and Bangladesh: carriers of AA had 56-58% and carriers of GA had 22% higher urinary Cd concentrations than GG. The consistency of the results in two different populations hints at a causal relation. Further, we found (2) that SNPs in the zinc-related genes SLC39A14 and SLC39A8 were associated with blood Cd concentrations, for SLC39A14 this may occur via differential gene expression. Finally, we found (3) that AA carriers of rs11076161 MT1A had higher Cd concentrations in blood among individuals in the highest Cd exposure group. Also, with increasing Cd exposure, carriers of this genotype experienced more Cd-related kidney toxicity. The present data are of significance for the theoretic understanding of the metabolism and toxicology of Cd, and, at the same time they are valuable in risk assessment, an issue of great importance, in light of the non-existing range between present exposure to Cd and toxicity in many parts of the world, including Sweden.
|
|
| 10. |
- Rentschler, Gerda, et al.
(författare)
-
Katalysatorelement (platina, palladium och rodium) i blod hos unga kvinnor i Skåne samt Norr- och Västerbotten : Slutrapport för projekt 215 0402 inom Nationella Miljöövervakningen
- 2007
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- De tre "katalysator-elementen" platina (Pt), palladium (Pd) och rodium (Rh), som emitteras från katalysatorer i bilarnas avgassystem, har undersökts i blodprover från 100 unga (20-29 år) kvinnor från Norr- ochVästerbotten (2004) och Skåne (2006-2007). Proverna har analyserats med mycket känslig och specifik, högupplösande induktivt kopplad plasma massspektrometri (HR-ICP-MS). Vi fann att genomsnittlig halt av Pt i blod (B-Pt) var 1-2 (högsta värde: 5) ng/L. B-Pd var i genomsnitt <10 (högsta värde: 33) ng/L; om mätvärden under den formella detektionsgränsen beaktas var genomsnittet 7 ng/L. B-Rh var i genomsnitt <5 (samtliga värden <5) ng/L; om värden under den formella detektionsgränsen beaktades, var genomsnittet 1 ng/L. Kvinnorna i Norr- och Västerbotten hade högre B-Pt och B-Pd (men inte B-Rh) än de i Skåne. Det skulle kunna bero på en skillnad i exponering (från emissioner från katalysatorer, miljön eller tandvårdsmaterial), eller på att exponeringen sjunkit mellan 2004 och 2006-2007. Dock måste stor reservation knytas till sådana slutsatser. Det är mer troligt att det beror på att proverna togs i olika rör. Det kan alltså föreligga en viss kontaminering i rören som användes 2004. Vidare - hade emission från bilars katalysatorer varit en viktig exponeringskälla, borde halten vara högre i det biltäta Skåne jämfört med Norr- och Västerbotten. Det fanns ingen säker effekt av ålder, och ingen effekt av rökvanor. Det finns inga skäl att tro att halterna av Pt, Pd eller Rh skulle innebära hälsorisk för kvinnorna. Dessa halter är mycket lägre än vad som tidigare rapporterats. Detta beror säkerligen på att den använda provtagnings- och analysmetodiken varit mycket känsligare. Vi har alltså anledning hävda, att tidigare studier starkt övervärderat halterna. Detta visar vikten av att använda adekvat analysmetodik. Det finns anledning att med tillräckligt känslig metodik följa upp halterna i olika geografiska områden, och att följa utvecklingen över tid, eftersom miljökontamineringen kan förväntas variera och öka.
|
|
