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- Kang, Xiaoying, et al.
(author)
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Association between Microscopic Colitis and Parkinson's Disease in a Swedish Population
- 2021
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In: Neurology. - : Wolters Kluwer. - 0028-3878 .- 1526-632X. ; 96:15 Suppl.
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Journal article (other academic/artistic)abstract
- Objective: To examine the association between microscopic colitis (MC) and Parkinson’s disease (PD) risk.Background: Gastrointestinal inflammation has been linked with PD. MC is a chronic intestinal inflammatory disease; however, its relationship with PD is unknown.Design/Methods: A population-based matched cohort study was conducted to estimate the association between MC and incident PD diagnosis using Cox regression models. An exposed cohort of 12,609 MC patients diagnosed 1990–2017 and aged ≥35 years at diagnosis was identified from the Epidemiology Strengthened by histoPathology Reports in Sweden cohort (ESPRESSO). Two unexposed cohorts were compared to: a population cohort comprising 58,879 MC-free individuals randomly selected from the population and 1:5 matched to each MC patient by age, sex, year of biopsy and county of residence at the time of biopsy; and a sibling cohort (NMC/NSibling=6,281/12,351) including all siblings of the MC patients. Follow-up was from the date of biopsy until December 31st 2016 at latest.Results: During a mean follow-up of ~7 years, we identified 449 incident PD diagnoses among the MC patients and their matched population cohort. The overall PD risk was 76% higher among MC versus MC-free individuals; but the association attenuated substantially during follow-up. In the time-varying effects model, PD risk was 3.45-fold (95% CI: 2.42, 4.93) higher during the first 2 years after biopsy and 1.80-fold (95% CI: 1.23, 2.64) higher during the following 3 years among MC versus MC-free individuals, but was not differential beyond 5 years after biopsy (hazard ratio=1.03; 95% CI: 0.68, 1.54). This temporal pattern of MC-PD associations persisted in sibling analyses. Using a matched case-control design, we also observed a higher prevalence of prior PD diagnosis among MC patients than the matched MC-free individuals (odds ratio=3.46; 95% CI: 2.91, 4.12).Conclusions: Our findings suggest that MC may not be a risk factor, but rather a comorbidity or complication of PD.
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| 2. |
- Wirdefeldt, Karin
(author)
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Studies of genetic and environmental influences on Parkinson’s disease
- 2004
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Doctoral thesis (other academic/artistic)abstract
- Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. Little is known about the etiology of PD. Although several PD genes are known, these are thought to be involved in only a small proportion of all PD cases. Some environmental exposures are associated with PD, but there are few consistent findings. The overall aim of this thesis was to examine genetic and environmental factors of importance for PD. In 12 families with autosomal dominant PD, linkage analyses were performed for 11 candidate loci associated with inherited diseases with clinical symptoms similar to PD or coding for proteins whose function might suggest involvement in the disease mechanism. Parametric lod scores were negative and non-parametric lod scores were close to zero. Nine of the 11 loci were excluded under an autosomal dominant model with reduced penetrance. There was no evidence for linkage to the examined loci considering the non-parametric results, although linkage could not be excluded. A few families showed positive lod scores indicating possible genetic heterogeneity. a-Synuclein was the first gene genetically linked to PD. In cerebral cortex from eight patients with Lewy body disease and nine controls, the expression of a-Synuclein was assessed using mRNA in situ hybridization. The a-Synuclein probe labeled pyramidal-like cells in lamina III and V in both patients and controls. There was no difference in a-Synuclein mRNA levels between patients and controls, and among patients there was no relationship between a-Synuclein mRNA and number of Lewy bodies. Thus, up regulation of the a-Synuclein gene alone does not seem to explain the accumulation of the protein in Lewy bodies. Heritability of PD was evaluated using the Swedish Twin Registry. PD cases were identified through telephone interviews and the Inpatient Discharge Register. In total 247 twins with self-reported PD or a PD diagnosis in the Inpatient Discharge Register were identified. There were only two concordant pairs. Thus, environmental factors appear to be most important in the etiology of clinically diagnosed PD. In a co-twin control study that controls for confounding by genetic and familial environmental factors, the association between smoking and PD was evaluated. Exposure information was obtained prospectively and PD cases (N=476) were identified through the Inpatient Discharge Register and the Cause of Death Register. When controlling for alcohol, coffee and education there was an inverse association between smoking and PD using unrelated controls as well as co-twin controls. Thus, the protective effect of smoking on PD was confirmed. The association does not appear to be explained solely by genetic and familial environmental factors. This thesis highlights the fact that PD most likely is influenced by various genetic and environmental factors. The failure to demonstrate linkage to any of the candidate loci in the PD families indicates that other genes may be involved. As shown by the twin data, environmental factors are most important for sporadic PD. Exploring interactions between genetic and environmental factors represents a challenge in future studies of PD.
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