Association Between Parkinsonʼs Disease and Inflammatory Bowel Disease

Lin, Ji-Ping; Lin, Chin; Hsu, Chin Wang; Lin, Cheng Li; Kao, Chia Hung

doi:10.1097/mib.0000000000000735

Cited by 163 publications

(145 citation statements)

References 38 publications

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“…2) in both Ashkenazi Jewish and non-Jewish datasets. Intriguingly, a recent independent report has suggested that PD is associated with an increased risk of IBD (34). Taken together, these results point toward potential shared genetic and epidemiological links between these two diseases and can help to identify a subgroup of patients with CD who are at a higher risk for developing PD.…”

Section: Discussionmentioning

confidence: 99%

Functional variants in the LRRK2 gene confer shared effects on risk for Crohn’s disease and Parkinson’s disease

et al. 2018

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Crohn’s disease (CD), a form of inflammatory bowel disease, has a higher prevalence in Ashkenazi Jewish than in non-Jewish European populations. To define the role of non-synonymous mutations, we performed exome sequencing of Ashkenazi Jewish patients with CD, followed by array-based genotyping and association analysis in 2,066 CD cases and 3,633 healthy controls. We detected association signals in the LRRK2 gene that conferred CD risk (N2081D variant, P=9.5×10−10) or protection (N551K variant, tagging R1398H-associated haplotype, P=3.3×10−8). These variants affected CD age of onset, disease location, LRRK2 activity, and autophagy. Bayesian network analysis of CD patient intestinal tissue further implicated LRRK2 in CD pathogenesis. Analysis of the extended LRRK2 locus in 24,570 CD cases, patients with Parkinson’s disease (PD), and healthy controls revealed extensive pleiotropy, with similar genetic effects between CD and PD in both Ashkenazi Jewish and non-Jewish cohorts. The LRRK2 N2081D CD risk allele is located in the same kinase domain as G2019S, a mutation that is the major genetic cause of familial and sporadic PD. Like the G2019S mutation, the N2081D variant is associated with increased kinase activity, whereas neither N551K nor R1398H on the protective haplotype altered kinase activity. R1398H, but not N551K, increased GTPase activity, thereby deactivating LRRK2. The presence of shared LRRK2 alleles in CD and PD provides refined insight into disease mechanisms and may have major implications for the treatment of these two seemingly unrelated diseases.

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Section: Discussionmentioning

confidence: 99%

Functional variants in the LRRK2 gene confer shared effects on risk for Crohn’s disease and Parkinson’s disease

et al. 2018

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“…The LHID 2000 was randomly sampled from the Registry for Beneficiaries and contains original claims data of one million beneficiaries enrolled in 2000. The details of the NHI program and LHID 2000 have been described in previous studies [19, 20]. The diagnoses in the LHID 2000 are coded on the basis of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM).…”

Section: Methodsmentioning

confidence: 99%

Lower Urinary Tract Infection and Subsequent Risk of Prostate Cancer: A Nationwide Population-Based Cohort Study

et al. 2017

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PurposeWe investigated whether lower urinary tract infection (LUTI), including cystitis or urethritis, is associated with an increased risk of developing prostate cancer (PCa), in a nationwide population-based cohort study.MethodsWe identified 14,273 men newly diagnosed with LUTI (9347 with cystitis, and 4926 with urethritis) between 1998 and 2011, from the Taiwan Longitudinal Health Insurance Database 2000. Each patient was randomly frequency-matched with 4 men without LUTI, based on age and index year of diagnosis. Cox’s proportional hazard regression analysis was performed to estimate the effect of LUTI on the PCa risk.ResultsThe risk of developing PCa was significantly higher in the cystitis cohort (adjusted HR = 1.46, 95% CI = 1.20–1.78) and in the urethritis cohort (adjusted HR = 1.72, 95% CI = 1.26–2.34) than in the group without LUTI. Further analyses indicated that patients with more than 5 medical visits for LUTI per year had a significantly greater risk of developing PCa.ConclusionWe found that cystitis or urethritis may play an etiological role in the development of PCa in Taiwanese men, particularly in those with repeated medical visits for cystitis or urethritis. Further studies are warranted on the association between LUTI and PCa in other countries, particularly where the prevalence of PCa is high.

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“…Remarkably, genomewide association studies identified leucine-rich repeat kinase 2 (LRRK2), the most common gene implicated in the pathogenesis of autosomal dominant PD, as one of the susceptibility genes for Crohn's disease [5]. These genetic data have been supported by a recent Taiwanese epidemiological study, which reported an increased risk of PD among individuals with Crohn's disease [6].…”

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confidence: 92%

LRRK2 Expression in the Enteric Nervous System: ENSuring Its Significance

Derkinderen

2017

Dig Dis Sci

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Association Between Parkinsonʼs Disease and Inflammatory Bowel Disease

Abstract: We suggest that IBD is associated with an increased risk of PD. Patients with IBD should be aware of the potential risk for PD development.

Cited by 163 publications

References 38 publications

Functional variants in the LRRK2 gene confer shared effects on risk for Crohn’s disease and Parkinson’s disease

Functional variants in the LRRK2 gene confer shared effects on risk for Crohn’s disease and Parkinson’s disease

Lower Urinary Tract Infection and Subsequent Risk of Prostate Cancer: A Nationwide Population-Based Cohort Study

LRRK2 Expression in the Enteric Nervous System: ENSuring Its Significance

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