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Träfflista för sökning "WFRF:(Westerlund Marie) srt2:(2005-2009)"

Sökning: WFRF:(Westerlund Marie) > (2005-2009)

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1.
  • Belin, Andrea Carmine, et al. (författare)
  • Association study of two genetic variants in mitochondrial transcription factor A (TFAM) in Alzheimer's and Parkinson's disease.
  • 2007
  • Ingår i: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 420:3, s. 257-62
  • Tidskriftsartikel (refereegranskat)abstract
    • Mitochondrial (mt) dysfunction has been implicated in Alzheimer's (AD) and Parkinson's disease (PD). Mitochondrial transcription factor A (TFAM) is needed for mtDNA maintenance, regulating mtDNA copy number and is absolutely required for transcriptional initiation at mtDNA promoters. Two genetic variants in TFAM have been reported to be associated with AD in a Caucasian case-control material collected from Germany, Switzerland and Italy. One of these variants was reported to show a tendency for association with AD in a pooled Scottish and Swedish case-control material and the other variant was reported to be associated with AD in a recent meta-analysis. We investigated these two genetic variants, rs1937 and rs2306604, in an AD and a PD case-control material, both from Sweden and found significant genotypic as well as allelic association to marker rs2306604 in the AD case-control material (P=0.05 and P=0.03, respectively), where the A-allele appears to increase risk for developing AD. No association was observed for marker rs1937. We did not find any association in the PD case-control material for either of the two markers. The distribution of the two-locus haplotype frequencies (based on rs1937 and rs2306604) did not differ significantly between affected individuals and controls in the two sample sets. However, the global P-value for haplotypic association testing indicated borderline association in the AD sample set. Our data suggests that the rs2306604 A-allele could be a moderate risk factor for AD, which is supported by the recent meta-analysis.
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2.
  • Carmine Belin, Andrea, et al. (författare)
  • Leucine-rich repeat kinase 2 (LRRK2) mutations in a Swedish Parkinson cohort and a healthy nonagenarian.
  • 2006
  • Ingår i: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 0885-3185. ; 21:10, s. 1731-4
  • Tidskriftsartikel (refereegranskat)abstract
    • Specific variants of Leucine-rich repeat kinase 2 (LRRK2) have been shown to associate with Parkinson's disease (PD). Several mutations have been found in PD populations from different parts of the world. We investigated the occurrence of three mutations (R1441G/C/H, G2019S, and I2020T) in our Swedish case-control material and identified four carriers of the G2019S mutation in 284 PD cases and 1 95-year-old carrier in 305 controls. The other two variants were absent in our material. We conclude that the LRRK2 G2019S mutation constitutes a significant factor for PD in the Swedish population and that it is not completely penetrant.
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3.
  • Carmine Belin, Andrea, et al. (författare)
  • S18Y in ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) associated with decreased risk of Parkinson's disease in Sweden.
  • 2007
  • Ingår i: Parkinsonism & related disorders. - : Elsevier BV. - 1353-8020. ; 13:5, s. 295-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is a neuron-specific enzyme that removes ubiquitin from the C-terminal end of substrates and a component of the ubiquitin-proteasome system. A protective effect of a UCH-L1 variant, S18Y, was suggested since the common variant was found to be inversely associated with sporadic Parkinson's disease (PD). We investigated the association of S18Y in our Swedish PD material. The tyrosine variant was significantly inversely associated with PD (P=0.049) and with a low age of onset (50 years) (P=0.017) in the case-control material, supporting the hypothesis of a protective function.
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4.
  • Melchior, Maria, et al. (författare)
  • Using sickness absence records to predict future depression in a working population : prospective findings from the GAZEL cohort.
  • 2009
  • Ingår i: American journal of public health. - 1541-0048. ; 99:8, s. 1417-22
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: We tested the hypothesis that sickness absence from work predicts workers' risk of later depression. METHODS: Study participants (n = 7391) belonged to the French GAZEL cohort of employees of the national gas and electricity company. Sickness absence data (1996-1999) were obtained from company records. Participants' depression in 1996 and 1999 was assessed with the Center for Epidemiologic Studies-Depression (CES-D) scale. The analyses were controlled for baseline age, gender, marital status, occupational grade, tobacco smoking status, alcohol consumption, subthreshold depressive symptoms, and work stress. RESULTS: Among workers who were free of depression in 1996, 13% had depression in 1999. Compared with workers with no sickness absence during the study period, those with sickness absence were more likely to be depressed at follow-up (for 1 period of sickness absence, fully adjusted odds ratio [OR] = 1.53, 95% confidence interval [CI] = 1.28, 1.82; for 2 or more periods, fully adjusted OR = 1.95, 95% CI = 1.61, 2.36). Future depression was predicted both by psychiatric and nonpsychiatric sickness absence (fully adjusted OR = 3.79 [95% CI = 2.81, 5.10] and 1.41 [95% CI = 1.21, 1.65], respectively). CONCLUSIONS: Sickness absence records may help identify workers vulnerable to future depression.
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5.
  • Vahtera, Jussi, et al. (författare)
  • Effect of retirement on sleep disturbances : the GAZEL prospective cohort study.
  • 2009
  • Ingår i: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 32:11, s. 1459-66
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Changes in health following retirement are poorly understood. We used serial measurements to assess the effect of retirement on sleep disturbances. DESIGN: Prospective cohort study. SETTING: The French national gas and electricity company. PARTICIPANTS: Fourteen thousand seven hundred fourteen retired employees (79% men). MEASUREMENTS AND RESULTS: Annual survey measurements of sleep disturbances ranging from 7 years before to 7 years after retirement (a mean of 12 measurements). Before retirement 22.2% to 24.6% of participants reported having disturbed sleep. According to repeated-measures logistic-regression analysis with generalized estimating equations estimation, the odds ratio (OR) for having a sleep disturbance in the postretirement period was 0.74 (95% confidence interval 0.71-0.77), compared with having a sleep disturbance in the preretirement period. The postretirement improvement in sleep was more pronounced in men (OR 0.66 [0.63-0.69]) than in women (OR 0.89 [0.84-0.95]) and in higher-grade workers than lower-grade workers. Postretirement sleep improvement was explained by the combination of preretirement risk factors suggesting removal of work-related exposures as a mechanism. The only exception to the general improvement in sleep after retirement was related to retirement on health grounds. In this group of participants, there was an increase in sleep disturbances following retirement. CONCLUSIONS: Repeated measurements provide strong evidence for a substantial and sustained decrease in sleep disturbances following retirement. The possibility that the health and well-being of individuals are significantly worse when in employment than following retirement presents a great challenge to improve the quality of work life in Western societies in which the cost of the aging population can only be met through an increase in average retirement age.
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6.
  • Westerlund, Hugo, et al. (författare)
  • Self-rated health before and after retirement in France (GAZEL) : a cohort study.
  • 2009
  • Ingår i: Lancet. - 1474-547X. ; 374:9705, s. 1889-96
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Governments need to increase the proportion of the population in work in most developed countries because of ageing populations. We investigated longitudinally how self-perceived health is affected by work and retirement in older workers. METHODS: We examined trajectories of self-rated health in 14 714 employees (11 581 [79%] men) from the French national gas and electricity company, the GAZEL cohort, for up to 7 years before and 7 years after retirement, with yearly measurements from 1989 to 2007. We analysed data by use of repeated-measures logistic regression with generalised estimating equations. FINDINGS: Overall, suboptimum health increased with age. However, between the year before retirement and the year after, the estimated prevalence of suboptimum health fell from 19.2% (95% CI 18.5-19.9) to 14.3% (13.7-14.9), corresponding to a gain in health of 8-10 years. We noted this retirement-related improvement in men (odds ratio 0.68, 95% CI 0.64-0.73) and women (0.74, 0.67-0.83), and across occupational grades (low 0.72, 0.63-0.82; high 0.70, 0.63-0.77), and it was maintained throughout the 7 years after retirement. A poor work environment and health complaints before retirement were associated with a steeper yearly increase in the prevalence of suboptimum health while still in work, and a greater retirement-related improvement; however, people with a combination of high occupational grade, low demands, and high satisfaction at work showed no such retirement-related improvement. INTERPRETATION: These findings suggest that the burden of ill-health, in terms of perceived health problems, is substantially relieved by retirement for all groups of workers apart from those with ideal working conditions, and that working life for older workers needs to be redesigned to achieve higher labour-market participation. FUNDING: Swedish Council for Working Life and Social Research, Academy of Finland, INSERM (France), BUPA Foundation (UK), European Science Foundation, and Economic and Social Research Council (UK).
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7.
  • Westerlund, Marie, et al. (författare)
  • Association of a polymorphism in the ABCB1 gene with Parkinson's disease.
  • 2009
  • Ingår i: Parkinsonism & related disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 15:6, s. 422-424
  • Tidskriftsartikel (refereegranskat)abstract
    • The ATP-binding cassette, sub-family B, member 1 (ABCB1) gene encoding the protein P-glycoprotein (P-gp) has been implicated in the pathophysiology of Parkinson's disease (PD) due to its role in regulating transport of endogenous molecules and exogenous toxins. In the present study, we analyzed the ABCB1 single nucleotide polymorphisms (SNPs) 1236C/T (exon 12), 2677G/T/A (exon 21) and 3435C/T (exon 26) in 288 Swedish PD patients and 313 control subjects and found a significant association of SNP 1236C/T with disease (p=0.0159; chi(2)=8.28), whereas the distributions of wild-type and mutated alleles were similar for 2677G/T/A and 3435C/T in patients and controls. Haplotype analysis revealed significant association of the 1236C-2677G haplotype with PD (p=0.026; chi(2)=4.955) and a trend towards association with disease of the 1236C-2677G-3435C haplotype (p=0.072; chi(2)=3.229). Altered ABCB1 and/or P-pg expression was recently shown in PD patients, and impaired drug efflux across barriers such as the gastrointestinal and nasal mucosal linings or the blood-brain barrier, might result in accumulation of drugs and/or endogenous molecules in toxic amounts, possibly contributing to disease. ABCB1 polymorphisms thus constitute an example of how genetic predisposition and environmental influences may combine to increase risk of PD.
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8.
  • Westerlund, Marie, et al. (författare)
  • Cerebellar alpha-synuclein levels are decreased in Parkinson's disease and do not correlate with SNCA polymorphisms associated with disease in a Swedish material.
  • 2008
  • Ingår i: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - : Wiley. - 1530-6860. ; 22:10, s. 3509-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Alterations of brain and plasma alpha-synuclein levels and SNCA gene variability have been implicated in the pathogenesis of Parkinson's disease (PD). We therefore measured alpha-synuclein protein levels in postmortem PD and control cerebellum tissue using Western blot and investigated whether the levels correlated to SNCA genotype. We found markedly decreased alpha-synuclein levels in PD patients (n=16) compared to gender- and age-matched controls (n=14; P=0.004) normalized to alpha-tubulin. We also performed an association study of the noncoding polymorphisms rs2737029 (A/G) and rs356204 (A/G) (intron 4), and of rs356219 (T/C) (3'-region) of SNCA in a Swedish PD case-control material. Using a two-sided chi(2) test, we found significant association of rs2737029 (P=0.003; chi(2)=9.07) and rs356204 (P=0.048; chi(2)=3.91) with disease, strengthening the involvement of SNCA polymorphisms in sporadic PD. Stratification of the human postmortem brain material by genotype of the three investigated polymorphisms, did not indicate any influence of genotype on alpha-synuclein protein levels when comparing PD with controls. Taken together, our findings demonstrate that the investigated Parkinson patients have markedly reduced levels of alpha-synuclein in cerebellum, and that this reduction is general, rather then correlated to the investigated polymorphisms, although two of the polymorphisms also associated with disease in a Swedish material.
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9.
  • Westerlund, Marie (författare)
  • On the roles of genes in Parkinson's disease
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Parkinson’s disease is a progressive neurodegenerative disorder which affects 1% of the population over the age of 60. In order to identify candidate genes with a potential role in Parkinson’s disease pathology, we investigated genes which are involved in protein aggregation and the ubiquitin‐proteasome system (α‐synuclein and ubiquitin carboxy‐terminal hydrolase L1, UCH‐L1), oxidative stress (DJ‐1), mitochondrial function (mitochondrial transcription factor A, TFAM), regulation of drug/toxin levels (multi‐drug resistance 1, MDR1 and alcohol and aldehyde dehydrogenases, ADH and ALDHs), as well as a gene with unknown function, but highly implicated in Parkinson’s disease genetics (leucine‐rich repeat kinase 2, LRRK2). (1) Using in situ hybridization, we characterized the cellular localization of candidate genes in both human and rodent tissues and found marked diversity in terms of areas and intensities of transcriptional activity. Some genes exhibited a widespread neuronal expression (UCH‐L1, DJ‐1, SNCA), one showed a particularly high expression in the dopamine target area striatum (LRRK2), some were expressed also in non‐neuronal tissues (LRRK2, DJ‐1, MDR1), and others exclusively so (ADH1, ADH4). (2) We also searched for genetic variability in a Swedish case‐control sample consisting of 310 Parkinson patients and 315 controls, which resulted in identification of several potential risk factors (LRRK2 G2019S; MDR1 1236C/T; SNCA rs2737029 (A/G) and rs356204 (A/G), as well as protective factors (UCH‐L1 S18Y) for disease. (3) Behavior, gene expression and/or brain neurotransmitter levels were studied in different transgenic and drug‐induced rodent models (Adh4‐/‐; α‐synuclein over expressing and α‐synuclein‐/‐; Darpp‐32‐/‐ and Darpp‐32 T34A mutant and MitoPark mice and in 6‐OHDA treated rats). A possible co‐regulation between Lrrk2 and α‐synuclein gene activities was found. Moreover, Adh4‐/‐ mice displayed alterations in substantia nigra dopamine levels, as well as in dopamine‐related behavior. In conclusion, the findings in the present thesis suggest an important role for genetic risk factors in the pathogenesis of Parkinson’s disease. Due to the great complexity of the disease, it seems likely that several molecular pathways and networks involving different genes and downstream effectors can affect the trophic support and/or survival of dopamine neurons, subsequently leading to Parkinson’s disease.
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