| 1. |
- Engström, Karin, et al.
(author)
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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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In: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 10:33
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Journal article (peer-reviewed)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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| 2. |
- Wennberg, Maria, 1974-, et al.
(author)
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Fish consumption and myocardial infarction : a second prospective biomarker study from northern Sweden
- 2011
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In: American Journal of Clinical Nutrition. - : American Society for Nutrition. - 0002-9165 .- 1938-3207. ; 93:1, s. 27-36
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Journal article (peer-reviewed)abstract
- Background: A beneficial role of fish consumption on the risk of myocardial infarction (MI) has been reported, mostly ascribed to n-3 fatty acids. However, fish also contains methylmercury, which may increase the risk of MI.Objective: Describe how fish consumption and erythrocyte concentrations of mercury (Ery-Hg) and selenium (Ery-Se) are related to the risk of MI, and whether n-3 fatty acids (eicosapentaenoic and docosahexaenoic acid) in plasma phospholipids (P-EPA+DHA) are protective.Design: This is a case-control study nested within the northern Sweden cohort with prospectively collected data and samples. It comprises 431 cases with an MI after data and sample collection, including 81 sudden cardiac deaths (SCD), and 499 matched controls. Another 69 female cases with controls from a breast cancer screening registry were included in sex-specific analyses.Results: Odds ratio (OR) for the third tertile versus the first were for Ery-Hg: 0.65 (95% CI: 0.46, 0.91); Ery-Se: 0.75 (95% CI: 0.53, 1.06) and P-EPA+DHA: 0.78 (95% CI: 0.54, 1.11). No association was seen for reported fish consumption. Multivariate modelling did not change these associations significantly. Sex-specific analyses revealed no differences in risk associations for Ery-Hg, but a tendency to a higher protective association with P-EPA+DHA for women. High levels of Ery-Se were associated with increased risk of SCD.Conclusions: Ery-Hg, a stable biomarker for fish consumption, is associated with a decreased risk of MI. The result indicates a protective effect of fish consumption against MI, even though data on self-reported fish consumption do not reveal any clear protective association.
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| 3. |
- Wennberg, Maria, 1974-, et al.
(author)
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Fish intake, mercury, long-chain n-3 polyunsaturated fatty acids and risk of stroke in northern Sweden
- 2007
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In: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 98:5, s. 1038-1045
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Journal article (peer-reviewed)abstract
- Results of previous studies on fish intake and stroke risk have been inconclusive. Different stroke types have often not been separated. Our aim was to elucidate whether intake of fish, Hg or the sum of proportions of fatty acids EPA (20:5n-3) and DHA (22: 6n-3) influence the risk of haemorrhagic or ischaemic stroke. Within a population-based cohort from a community intervention programme, 369 stroke cases and 738 matched controls were identified and included in the present nested case-control study. Information on fish intake had been recorded at recruitment, i.e. before diagnosis. Hg levels were determined in erythrocyte membranes, also collected at recruitment, and the relative content of fatty acids was measured in erythrocyte membranes or plasma phospholipids. The results showed that in women there was a non-significant decrease in stroke risk with increasing fish intake (OR 0·90 (95 % CI 0·73, 1-11) per meal per week). The risk in women differed significantly (P=0·03) from that in men, in whom the OR for stroke rose with increasing fish intake (OR 1·24 (95 % CI 1·01, 1·51) per meal per week). The corresponding risk in men for Hg was 0·99 (95 % CI 0·93, 1·06), and for the sum of proportions of EPA and DHA 1·08 (95 % CI 0·92, 1·28). We conclude that the relationship between stroke risk and fish intake seems to be different in men and women. Increased levels of EPA and DHA do not decrease the risk for stroke and there is no association between stroke risk and Hg at these low levels.
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| 4. |
- Wennberg, Maria, et al.
(author)
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Myocardial infarction in relation to mercury and fatty acids from fish : a risk-benefit analysis based on pooled Finnish and Swedish data in men
- 2012
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In: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 96:4, s. 706-713
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Journal article (peer-reviewed)abstract
- Background: Exposure to methylmercury from fish has been associated with increased risk of myocardial infarction (MI) in some studies. At the same time, marine n-3 (omega-3) PUFAs are an inherent constituent of fish and are regarded as beneficial. To our knowledge, no risk-benefit model on the basis of data on methylmercury, PUFA, and MI risk has yet been presented.Objective: The objective of this study was to describe how exposure to both marine n-3 PUFAs and methylmercury relates to MI risk by using data from Finland and Sweden.Design: We used matched case-control sets from Sweden and Finland that were nested in population-based, prospective cohort studies. We included 361 men with MI from Sweden and 211 men with MI from Finland. MI risk was estimated in a logistic regression model with the amount of mercury in hair (hair-Hg) and concentrations of n-3 PUFAs (EPA and DHA) in serum (S-PUFA) as independent variables.Results: The median hair-Hg was 0.57 mu g/g in Swedish and 1.32 mu g/g in Finnish control subjects, whereas the percentage of S-PUFA was 4.21% and 3.83%, respectively. In combined analysis, hair-Hg was associated with higher (P = 0.005) and S-PUFA with lower (P = 0.011) MI risk. Our model indicated that even a small change in fish consumption (ie, by increasing S-PUFA by 1%) would prevent 7% of MIs, despite a small increase in mercury exposure. However, at a high hair-Hg, the modeled beneficial effect of PUFA on MI risk was counteracted by methylmercury.Conclusions: Exposure to methylmercury was associated with increased risk of MI, and higher S-PUFA concentrations were associated with decreased risk of MI. Thus, MI risk may be reduced by the consumption of fish high in PUFAs and low in methylmercury.Am J Clin Nutr 2012;96:706-13.
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