| 1. |
- Xu, Yiyi, et al.
(författare)
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Associations of blood mercury and fatty acid concentrations with blood mitochondrial DNA copy number in the Seychelles Child Development Nutrition Study
- 2019
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 124, s. 278-283
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fish contains methylmercury (MeHg) which can cause oxidative stress and neurodevelopmental toxicity at sufficiently high doses. Fish also contains polyunsaturated fatty acids (PUFA) which have both antioxidant (n-3) and oxidant (n-6) properties. Mitochondrial DNA (mtDNA) is sensitive to oxidative stress but has not been previously studied in relation to MeHg exposure or PUFA status. Objective: To investigate the associations between MeHg exposure and PUFA status during pregnancy with relative mitochondrial DNA copy number (RmtDNAcn) in mothers and their newborns. Methods: In total, 1488 mother-child pairs from the Seychelles Child Development Study Nutrition Cohort 2 were included in this study. Total Hg was measured in maternal blood collected at 28 weeks' gestation, maternal hair at delivery, and in fetal cord blood. PUFA (n-3 and n-6) were measured only in maternal blood. RmtDNAcn was measured by qPCR in both maternal and cord blood. Results: Increasing maternal blood Hg (beta = 0.001, 95% CI: 0.000, 0.002) and n-3 PUFA concentrations (beta = 0.183, 95% CI: 0.048, 0.317) were associated with higher maternal RmtDNAcn. Increasing maternal n-6 PUFA (beta =-0.103, 95% CI: -0.145, -0.062) and n-6/n-3 ratio (beta =-0.011, 95% CI: -0.017, -0.004) were associated with lower maternal RmtDNAcn. Increasing fetal cord blood Hg was associated with lower fetal RmtDNAcn (beta =-0.002, 95% CI: -0.004, -0.000). Neither maternal blood Hg nor PUFA status was associated with fetal RmtDNAcn. Conclusions: Our findings suggest that MeHg and PUFA may influence mitochondrial homeostasis although the magnitude of these associations are small. Future studies should confirm the findings and explore the underlying mechanisms.
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| 2. |
- Yeates, Alison J, et al.
(författare)
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Genetic variation in FADS genes is associated with maternal long-chain PUFA status but not with cognitive development of infants in a high fish-eating observational study.
- 2015
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Ingår i: Prostaglandins, Leukotrienes and Essential Fatty Acids. - : Elsevier BV. - 0952-3278 .- 1532-2823. ; 102-103, s. 13-20
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Forskningsöversikt (refereegranskat)abstract
- Long-chain n-6 and n-3 PUFA (LC-PUFA), arachidonic acid (AA) (20:4n-6) and DHA (22:6n-3), are critical for optimal brain development. These fatty acids can be consumed directly from the diet, or synthesized endogenously from precursor PUFA by Δ-5 (encoded by FADS1) and Δ-6 desaturases (encoded by FADS2). The aim of this study was to determine the potential importance of maternal genetic variability in FADS1 and FADS2 genes to maternal LC-PUFA status and infant neurodevelopment in populations with high fish intakes. The Nutrition Cohorts 1 (NC1) and 2 (NC2) are longitudinal observational mother-child cohorts in the Republic of Seychelles. Maternal serum LC-PUFA was measured at 28 weeks gestation and genotyping for rs174537 (FADS1), rs174561 (FADS1), rs3834458 (FADS1-FADS2) and rs174575 (FADS2) was performed in both cohorts. The children completed the Bayley Scales of Infant Development II (BSID-II) at 30 months in NC1 and at 20 months in NC2. Complete data were available for 221 and 1310 mothers from NC1 and NC2 respectively. With increasing number of rs3834458 minor alleles, maternal concentrations of AA were significantly decreased (NC1 p=0.004; NC2 p<0.001) and precursor:product ratios for linoleic acid (LA) (18:2n-6)-to-AA (NC1 p<0.001; NC2 p<0.001) and α-linolenic acid (ALA) (18:3n-3)-to-DHA were increased (NC2 p=0.028). There were no significant associations between maternal FADS genotype and BSID-II scores in either cohort. A trend for improved PDI was found among infants born to mothers with the minor rs3834458 allele.In these high fish-eating cohorts, genetic variability in FADS genes was associated with maternal AA status measured in serum and a subtle association of the FADS genotype was found with neurodevelopment.
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| 3. |
- Engström, Karin, et al.
(författare)
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Polymorphisms in ATP-binding cassette transporters associated with maternal methylmercury disposition and infant neurodevelopment in mother-infant pairs in the Seychelles Child Development Study
- 2016
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 94, s. 224-229
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Tidskriftsartikel (refereegranskat)abstract
- Background: ATP-binding cassette (ABC) transporters have been associated with methylmercury (MeHg) toxicity in experimental animal models. Aims: To evaluate the association of single nucleotide polymorphisms (SNPs) in maternal ABC transporter genes with 1) maternal hair MeHg concentrations during pregnancy and 2) child neurodevelopmental outcomes. Materials and methods: Nutrition Cohort 2 (NC2) is an observational mother-child cohort recruited in the Republic of Seychelles from 2008-2011. Total mercury (Hg) was measured in maternal hair growing during pregnancy as a biomarker for prenatal MeHg exposure (N = 1313) (mean 3.9 ppm). Infants completed developmental assessments by Bayley Scales of Infant Development II (BSID-II) at 20 months of age (N = 1331). Genotyping for fifteen SNPs in ABCC1, ABCC2 and ABCB1 was performed for the mothers. Results: Seven of fifteen ABC SNPs (ABCC1 rs11075290, rs212093, and rs215088; ABCC2 rs717620; ABCB1 rs10276499, rs1202169, and rs2032582) were associated with concentrations of maternal hair Hg (p < 0.001 to 0.013). One SNP (ABCC1 rs11075290) was also significantly associated with neurodevelopment; children born to mothers with rs11075290 CC genotype (mean hair Hg 3.6 ppm) scored on average 2 points lower on the Mental Development Index (MDI) and 3 points lower on the Psychomotor Development Index (PDI) than children born to mothers with TT genotype (mean hair Hg 4.7 ppm) while children with the CT genotype (mean hair Hg 4.0 ppm) had intermediate BSID scores. Discussion: Genetic variation in ABC transporter genes was associated with maternal hair Hg concentrations. The implications for MeHg dose in the developing child and neurodevelopmental outcomes need to be further investigated.
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| 4. |
- Wahlberg, Karin, et al.
(författare)
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Maternal polymorphisms in glutathione-related genes are associated with maternal mercury concentrations and early child neurodevelopment in a population with a fish-rich diet
- 2018
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 115, s. 142-149
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Glutathione (GSH) pathways play a key role the metabolism and elimination of the neurotoxicant methylmercury (MeHg). We hypothesized that maternal genetic variation linked to GSH pathways could influence MeHg concentrations in pregnant mothers and children and thereby also affect early life development. Methods: The GCLM (rs41303970, C/T), GCLC (rs761142, T/G) and GSTP1 (rs1695, A/G) polymorphisms were genotyped in 1449 mothers in a prospective study of the Seychellois population with a diet rich in fish. Genotypes were analyzed in association with maternal hair and blood Hg, fetal blood Hg (cord blood Hg), as well as children's mental (MDI) and motor development (PDI; MDI and PDI assessed by Bayley Scales of Infant Development at 20 months). We also examined whether genotypes modified the association between Hg exposure and developmental outcomes. Results: GCLC rs761142 TT homozygotes showed statistically higher mean maternal hair Hg (4.12 ppm) than G carriers (AG 3.73 and GG 3.52 ppm) (p = 0.037). For the combination of GCLC rs761142 and GCLM rs41303970, double homozygotes TT + CC showed higher hair Hg (4.40 ppm) than G + T carriers (3.44 ppm; p = 0.018). No associations were observed between GSTP1 rs1695 and maternal hair Hg or between any genotypes and maternal blood Hg or cord blood Hg. The maternal GSTP1 rs1695 rare allele (G) was associated with a lower MDI among children (β = −1.48, p = 0.048). We also observed some interactions: increasing Hg in maternal and cord blood was associated with lower PDI among GCLC rs761142 TT carriers; and increasing Hg in hair was associated with lower MDI among GSTP1 rs1695 GG carriers. Conclusions: Maternal genetic variation in genes involved in GSH synthesis is statistically associated with Hg concentrations in maternal hair, but not in maternal or fetal blood. We observed interactions that suggest maternal GSH genetics may modify associations between MeHg exposure and neurodevelopmental outcomes.
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| 5. |
- Yeates, Alison Jayne, et al.
(författare)
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Maternal Long-Chain Polyunsaturated Fatty Acid Status, Methylmercury Exposure, and Birth Outcomes in a High-Fish-Eating Mother-Child Cohort
- 2020
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Ingår i: The Journal of nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 150:7, s. 1749-1756
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Maternal status of long-chain PUFAs (LC-PUFAs) may be related to fetal growth. Maternal fish consumption exposes the mother to the neurotoxicant methylmercury (MeHg), which, in contrast, may restrict fetal growth. OBJECTIVE: Our aim was to examine relations between maternal LC-PUFA status at 28 wk and birth outcomes (birth weight, length, and head circumference), controlling for MeHg exposure throughout pregnancy, in the Seychelles Child Development Study Nutrition Cohort 2. Our secondary aim was to examine the influence of maternal variation in genes regulating the desaturation of LC-PUFAs [fatty acid desaturase (FADS)] on birth outcomes. METHODS: From nonfasting blood samples collected at 28 wk of gestation, we measured serum total LC-PUFA concentrations and FADS1 (rs174537, rs174561), FADS1-FADS2rs3834458, and FADS2rs174575 genotypes, with hair total mercury concentrations assessed at delivery. Data were available for n = 1236 mother-child pairs. Associations of maternal LC-PUFAs, MeHg, and FADS genotype with birth outcomes were assessed by multiple linear regression models, adjusting for child sex, gestational age, maternal age, BMI, alcohol use, socioeconomic status, and parity. RESULTS: In our cohort of healthy mothers, neither maternal LC-PUFA status nor MeHg exposure were significant determinants of birth outcomes. However, when compared with major allele homozygotes, mothers who were heterozygous for the minor allele of FADS1 (rs174537 and rs174561, GT compared with TT, β = 0.205, P = 0.03; TC compared with CC, β = 0.203, P = 0.04) and FADS1-FADS2 (rs3834458, Tdel compared with DelDel, β = 0.197, P = 0.04) had infants with a greater head circumference (all P < 0.05). Homozygosity for the minor allele of FADS2 (rs174575) was associated with a greater birth weight (GG compared with CC, β = 0.109, P = 0.04). CONCLUSIONS: In our mother-child cohort, neither maternal LC-PUFA status nor MeHg exposure was associated with birth outcomes. The observed associations of variation in maternal FADS genotype with birth outcomes should be confirmed in other populations.
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| 6. |
- Bohlin, I, et al.
(författare)
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Mapping potential location for bilberry picking with remote sensing, local field data andphone application
- 2023
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the study was to create a practical method for identifying potential locations for bilberry picking with help of remote sensing, local field data and phone application to support the development of the local berry value chain. Local field data w as collected 2021 and 2022 and consisted 503 and 525 plots from a study area of circa 25x45km in Västerbotten, Sweden. The potential for bilberry production was evaluated by measuring the shrub cover and amount of raw berries. Wall to wall remote sensing d ata included a Sentinel 2 image from same summer, airborne laser scanning data from 2020 and other map products. We created classification models for bilberry shrub and yield using both logistic regression (2 classes) and ordinal regression (3 classes) mod els using 2021 data, and validated and calibrated models with 2022 data. Predictor variables consisted of spectral metrics from satellite data; structural metrics from laser data; existing raster maps of tree species, stand attributes, site index, soil moi sture and land use classes. The 2 class models performed better than three class models, delivering the AUC 0.73, overall accuracy 0.83 and kappa value 0.51 for best bilberry shrub model and 0.75, 0.77 and 0.50 respectively for best bilberry yield model. T he best models included both laser based structural metrics describing e.g canopy closure and spectral metrics, but also e.g. volume of pine, soil moisture and site index were found significant predictor variables. Calibration of the models improved annual predictions and the validation of the 2021 raster maps with 2022 data produced similar AUC, OA, and kappa values for bilberry yield (0.73, 0.74 and 0.46), but lower for bilberry shrub (0.61, 0.68 and 0.24). A dedicated phone application was developed duri ng the project, which was used both for collecting the field data and for presenting the potential locations of berry yields. Local berry maps can help berry pickers easier to find the berries in forest landscape and therefore support local berry value cha in. This study is part of the FAIRCHAIN project, which has received funding from the European Union’s funding programme H2020 research and innovation programme under grand agreement 101000723.
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| 7. |
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| 8. |
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| 9. |
- Conway, Marie C, et al.
(författare)
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Maternal and child FADS genotype as determinants of cord blood long chain polyunsaturated fatty acid (LCPUFA) concentrations in the Seychelles Child Development Study
- 2021
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Ingår i: British Journal of Nutrition. - 1475-2662. ; 126:11, s. 1687-1697
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Tidskriftsartikel (refereegranskat)abstract
- Optimal maternal long chain polyunsaturated fatty acid (LCPUFA) status is essential for the developing foetus. The fatty acid desaturase (FADS) genes are involved in the endogenous synthesis of LCPUFA. The minor allele of various FADS single nucleotide polymorphisms (SNPs) have been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), and lower concentrations of arachidonic acid (AA) and docosahexaenoic acid (DHA). There is limited research on the influence of FADS genotype on cord PUFA status. The current study investigated the influence of maternal and child genetic variation in FADS genotype on cord blood PUFA status in a high fish-eating cohort. Cord blood samples (n=1088) collected from the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2) were analysed for total serum PUFA. Of those with cord PUFA data available, maternal (n=1062) and child (n=916), FADS1 (rs174537, rs174561), FADS2 (rs174575), and FADS1-FADS2 (rs3834458) were determined. Regression analysis determined that maternal minor allele homozygosity was associated with lower cord blood concentrations of docosahexaenoic acid (DHA) and the sum of EPA+DHA. Lower cord blood AA concentrations were observed in children who were minor allele homozygous for rs3834458 (β=0.075; p=0.037). Children who were minor allele carriers for rs174537, rs174561, rs174575 and rs3834458 had a lower cord blood AA:LA ratio (p<0.05 for all). Both maternal and child FADS genotype were associated with cord LCPUFA concentrations, and therefore, the influence of FADS genotype was observed despite the high intake of preformed dietary LCPUFA from fish in this population.
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| 10. |
- Conway, Marie C, et al.
(författare)
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The influence of fish consumption on serum n-3 polyunsaturated fatty acid (PUFA) concentrations in women of childbearing age : a randomised controlled trial (the iFish Study)
- 2021
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Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6215 .- 1436-6207. ; 60:3, s. 1415-1427
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Long-chain polyunsaturated fatty acids (LCPUFA) can be synthesised endogenously from linoleic acid (LA) and α-linolenic acid (ALA) in a pathway involving the fatty acid desaturase (FADS) genes. Endogenous synthesis is inefficient; therefore, dietary intake of preformed LCPUFA from their richest source of fish is preferred. This study investigated the effect of fish consumption on PUFA concentrations in women of childbearing age while stratifying by FADS genotype. The influence of fish consumption on lipid profile, and markers of inflammation and oxidative stress was also examined.METHODS: Healthy women (n = 49) provided a buccal swab which was analysed for FADS2 genotype (rs3834458; T/deletion). Participants were stratified according to genotype and randomised to an intervention group to receive either no fish (n = 18), 1 portion (n = 14) or 2 portions (n = 17) (140 g per portion) of fish per week for a period of 8 weeks. Serum PUFA was analysed at baseline and post-intervention. Lipid profile, and markers of inflammation and oxidative stress were also analysed.RESULTS: Participants consuming 2 portions of fish per week had significantly higher concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and total n-3 PUFA, and a lower n-6:n-3 ratio compared to those in the no fish or 1 portion per week group (all p < 0.05). Fish consumption did not have a significant effect on biomarkers of oxidative stress, inflammation and lipid profile in the current study.CONCLUSION: Consumption of 2 portions of fish per week has beneficial effects on biological n-3 PUFA concentrations in women of childbearing age; however, no effects on oxidative stress, inflammation or lipid profile were observed. This trial was registered at www.clinicaltrials.gov (NCT03765580), registered December 2018.
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| 11. |
- Love, Tanzy M, et al.
(författare)
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Contribution of child ABC-transporter genetics to prenatal MeHg exposure and neurodevelopment
- 2022
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Ingår i: NeuroToxicology. - : Elsevier BV. - 1872-9711 .- 0161-813X. ; 91, s. 228-233
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is emerging evidence that exposure to prenatal methylmercury (MeHg) from maternal fish consumption during pregnancy can differ between individuals due to genetic variation. In previous studies, we have reported that maternal polymorphisms in ABC-transporter genes were associated with maternal hair MeHg concentrations, and with children's early neurodevelopmental tests. In this study, we add to these findings by evaluating the contribution of genetic variation in children's ABC-transporter genes to prenatal MeHg exposure and early child neurodevelopmental tests.METHODS: We genotyped six polymorphisms (rs2032582, rs10276499 and rs1202169 in ABCB1; rs11075290 and rs215088 in ABCC1; rs717620 in ABCC2) in DNA from cord blood and maternal blood of the Seychelles Child Development Study Nutrition Cohort 2. We determined prenatal MeHg exposure by measuring total mercury (Hg) in cord blood by atomic fluorescence spectrometry. We assessed neurodevelopment in children at approximately 20 months using the Bayley Scales of Infant Development (BSID-II). We used linear regression models to analyze covariate-adjusted associations of child genotype with cord MeHg and BSID-II outcomes (Mental Developmental and Psychomotor Developmental Indexes). We also evaluated interactions between genotypes, cord MeHg, and neurodevelopmental outcomes. All models were run with and without adjustment for maternal genotype.RESULTS: Of the six evaluated polymorphisms, only ABCC1 rs11075290 was associated with cord blood MeHg; children homozygous for the T-allele had on average 29.99µg/L MeHg in cord blood while those homozygous for the C-allele had on average 38.06µg/L MeHg in cord blood (p<0.001). No polymorphisms in the children were associated with either subscale of the BSID. However, the association between cord MeHg and the Mental Developmental Index (MDI) of the BSID differed significantly across the three genotypes of ABCB1 rs10276499 (2df F-test, p=0.045). With increasing cord MeHg, the MDI decreased (slope=-0.091, p=0.014) among children homozygous for the rare C-allele.CONCLUSIONS: These findings support the possibility that child ABC genetics might influence prenatal MeHg exposure.
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| 12. |
- Taj, Tahir, et al.
(författare)
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Effect of welding fumes on the cardiovascular system: a six-year longitudinal study
- 2021
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Ingår i: Scandinavian Journal of Work Environment & Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 47:1, s. 52-61
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Tidskriftsartikel (refereegranskat)abstract
- Objective This study investigated whether low-to-moderate exposure to welding fumes is associated with adverse effects on the cardiovascular system. Methods To test this, we performed a longitudinal analysis of 78 mild steel welders and 96 controls; these subjects were examined twice, six years apart (ie, timepoints 1 and 2). All subjects (male and non-smoking at recruitment) completed questionnaires describing their health, work history, and lifestyle. We measured their blood pressure, endothelial function (by EndoPAT), and risk markers for cardiovascular disease [low-density lio-protein (LDL), homocysteine, C-reactive protein]. Exposure to welding fumes was assessed from the responses to questionnaires and measurements of respirable dust in their breathing zones adjusted for use of respiratory protection equipment. Linear mixed-effect regression models were used for the longitudinal analysis. Results Median respirable dust concentrations, adjusted for respirable protection, of the welders were 0.7 (5-95 percentile range 0.2-4.2) and 0.5 (0.1-1.9) mg/m 3 at timepoints 1 and 2, respectively. Over the six-year period, welders showed a statistically significant increase in systolic [5.11 mm Hg, 95% confidence interval (CI) 1.92-8.31] and diastolic (3.12 mm Hg, 95% CI 0.74-5.5) blood pressure compared with controls (multi-variable adjusted mixed effect models). Diastolic blood pressure increased non-significantly by 0.22 mm Hg (95% CI-0.02-0.45) with every additional year of welding work. No consistent significant associations were found between exposure and endothelial function, LDL, homocysteine, or C-reactive protein. Conclusion Exposure to welding fumes at low-to-moderate levels is associated with increased blood pressure, suggesting that reducing the occupational exposure limit (2.5 mg/m(3) for inorganic respirable dust in Sweden) is needed to protect cardiovascular health of workers.
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| 13. |
- Wahlberg, Karin E, et al.
(författare)
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Common polymorphisms in the solute carrier SLC30A10 are associated with blood manganese and neurological function.
- 2016
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-0929 .- 1096-6080. ; 149:2, s. 473-483
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Tidskriftsartikel (refereegranskat)abstract
- Manganese (Mn) is an essential nutrient in humans, but excessive exposure to Mn may cause neurotoxicity. Despite homeostatic regulation, Mn concentrations in blood vary considerably among individuals. We evaluated if common single-nucleotide polymorphisms (SNPs) in SLC30A10, which likely encodes a Mn transporter, influence blood Mn concentrations and neurological function. We measured blood Mn concentrations by ICP-MS or atomic absorption spectroscopy and genotyped two SLC30A10 non-coding SNPs (rs2275707 and rs12064812) by TaqMan PCR in cohorts from Bangladesh (N=406), the Argentinean Andes (N=198), and Italy (N=238). We also measured SLC30A10 expression in whole blood by TaqMan PCR in a sub-group (N=101) from the Andean cohort, and neurological parameters (sway velocity and finger-tapping speed) in the Italian cohort.The rs2275707 variant allele was associated with increased Mn concentrations in the Andes (8%, p=0.027) and Italy (10.6%, p=0.012), but not as clear in Bangladesh (3.4%, p=0.21; linear regression analysis adjusted for age, gender, and plasma ferritin). This allele was also associated with increased sway velocity (15%, p=0.033; adjusted for age and sex) and reduced SLC30A10 expression (-24.6%, p=0.029). By contrast, the rs12064812 variant homozygous genotype was associated with reduced Mn concentrations, particularly in the Italian cohort (-18.4%, p=0.04), and increased finger-tapping speed (8.7%, p=0.025).We show that common SNPs in SLC30A10 are associated with blood Mn concentrations in three unrelated cohorts and that their influence may be mediated by altered SLC30A10 expression. Moreover, the SNPs appeared to influence neurological functions independent of blood Mn concentrations, suggesting that SLC30A10 could regulate brain Mn levels.
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| 14. |
- Wahlberg, Karin E, et al.
(författare)
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Polymorphisms in Manganese Transporters SLC30A10 and SLC39A8 Are Associated With Children's Neurodevelopment by Influencing Manganese Homeostasis
- 2018
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Ingår i: Frontiers in Genetics. - : Frontiers Media SA. - 1664-8021. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Manganese (Mn) is an essential element but at excessive levels, it is neurotoxic. Even a moderate increase in Mn has been suggested to interfere with neurodevelopment in children. Genetics influencing Mn concentrations and toxicity is unclear. Objective: We assessed, in a cross-sectional study, whether common single-nucleotide polymorphisms in the Mn transporters SLC39A8 (influx) and SLC30A10 (efflux) are associated with neurodevelopment in children. Design: We genotyped SLC39A8 (rs13107325 C/T) and SLC30A10 (rs1776029 G/A and rs12064812 T/C) in Italian children (n = 686, ages 11-14). We then used linear regression models to analyze associations between genotype, blood Mn concentrations, and neurodevelopmental outcomes including intelligence, behavior, motor function, and sway. Inferred causal relationships were evaluated using instrumental variables (IV) analysis. Results: For SLC30A10 rs1776029, the minor allele (A) was associated with increased average blood Mn of 41% (p < 0.001), whereas minor alleles for rs12064812 (C) and rs13107325 (T) were associated with reduced blood Mn of 7% (p = 0.002) and 15% (p < 0.001), respectively. For children carrying genotypes associated with high blood Mn, we observed lower performance for certain IQ subtests, increased sway, and increased scores for behavioral problems. High Mn genotypes showed odds ratios of 2-4 (p ≤ 0.01) for high scores in tests assessing ADHD-related behavior. IV analyses suggested that several of the associations were mediated by blood Mn. Conclusions: Our results suggest that common polymorphisms in SLC39A8 and SLC30A10 influence neurodevelopmental outcomes in children via differences in Mn homeostasis.
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| 15. |
- Papakokkinou, Eleni, et al.
(författare)
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Excess Morbidity Persists in Patients With Cushing’s Disease During Long-term Remission : A Swedish Nationwide Study
- 2020
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - Washington : Oxford University Press. - 0021-972X .- 1945-7197. ; 105:8, s. 2616-2624
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Tidskriftsartikel (refereegranskat)abstract
- Context: Whether multisystem morbidity in Cushing's disease (CD) remains elevated during long-term remission is still undetermined.Objective: To investigate comorbidities in patients with CD.Design, setting, and patients: A retrospective, nationwide study of patients with CD identified in the Swedish National Patient Register between 1987 and 2013. Individual medical records were reviewed to verify diagnosis and remission status.Main outcomes: Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by using the Swedish general population as reference. Comorbidities were investigated during three different time periods: (i) during the 3 years before diagnosis, (ii) from diagnosis to 1 year after remission, and (iii) during long-term remission.Results: We included 502 patients with confirmed CD, of whom 419 were in remission for a median of 10 (interquartile range 4 to 21) years. SIRs (95% CI) for myocardial infarction (4.4; 1.2 to 11.4), fractures (4.9; 2.7 to 8.3), and deep vein thrombosis (13.8; 3.8 to 35.3) were increased during the 3-year period before diagnosis. From diagnosis until 1 year after remission, SIRs (95% CI were increased for thromboembolism (18.3; 7.9 to 36.0), stroke (4.9; 1.3 to 12.5), and sepsis (13.6; 3.7 to 34.8). SIRs for thromboembolism (4.9; 2.6 to 8.4), stroke (3.1; 1.8 to 4.9), and sepsis (6.0; 3.1 to 10.6) remained increased during long-term remission.Conclusion: Patients with CD have an increased incidence of stroke, thromboembolism, and sepsis even after remission, emphasizing the importance of early identification and management of risk factors for these comorbidities during long-term follow-up.
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| 16. |
- Ragnarsson, Oskar, 1971, et al.
(författare)
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The incidence of Cushing’s disease : a nationwide Swedish study
- 2019
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Ingår i: Pituitary. - : Springer. - 1386-341X .- 1573-7403. ; 22:2, s. 179-186
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies on the incidence of Cushing’s disease (CD) are few and usually limited by a small number of patients. The aim of this study was to assess the annual incidence in a nationwide cohort of patients with presumed CD in Sweden.Methods: Patients registered with a diagnostic code for Cushing’s syndrome (CS) or CD, between 1987 and 2013 were identified in the Swedish National Patient Registry. The CD diagnosis was validated by reviewing clinical, biochemical, imaging, and histopathological data.Results: Of 1317 patients identified, 534 (41%) had confirmed CD. One-hundred-and-fifty-six (12%) patients had other forms of CS, 41 (3%) had probable but unconfirmed CD, and 334 (25%) had diagnoses unrelated to CS. The mean (95% confidence interval) annual incidence between 1987 and 2013 of confirmed CD was 1.6 (1.4–1.8) cases per million. 1987–1995, 1996–2004, and 2005–2013, the mean annual incidence was 1.5 (1.1–1.8), 1.4 (1.0–1.7) and 2.0 (1.7–2.3) cases per million, respectively. During the last time period the incidence was higher than during the first and second time periods (P < 0.05).Conclusion: The incidence of CD in Sweden (1.6 cases per million) is in agreement with most previous reports. A higher incidence between 2005 and 2013 compared to 1987–2004 was noticed. Whether this reflects a truly increased incidence of the disease, or simply an increased awareness, earlier recognition, and earlier diagnosis can, however, not be answered. This study also illustrates the importance of validation of the diagnosis of CD in epidemiological research.
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