期刊
NEUROBIOLOGY OF AGING
卷 48, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2016.07.013
关键词
Parkinson's; Cutaneous malignant melanoma; Shared genetic background; Pigmentation; Tyrosinase
资金
- Intramural Research Programs of the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Aging (NIA), National Institutes of Health, Department of Health and Human Services [Z01-AG000949-02, Z01-ES101986]
- National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services [Z01-AG000949-02, Z01-ES101986]
- Department of Defence [W81XWH-09-2-0128]
- Michael J. Fox Foundation for Parkinson's Research
- National Institutes of Health [R01NS037167, R01CA141668, P50NS071674]
- American Parkinson Disease Association (APDA)
- Barnes-Jewish Hospital Foundation
- Greater St Louis Chapter of the APDA
- Hersenstichting Nederland
- Neuroscience Campus Amsterdam
- section of medical genomics, the Prinses Beatrix Fonds
- Forschungszentrum fur Umwelt und Gesundheit - German Federal Ministry of Education, Science, Research, and Technology
- State of Bavaria
- German National Genome Network (NGFNplus, German Ministry for Education and Research) [01GS08134]
- German Federal Ministry of Education and Research [NGFN 01GR0468]
- ERA-NET NEURON [01EW0908]
- Helmholtz Alliance Mental Health in an Ageing Society - Initiative and Networking Fund of the Helmholtz Association [HA-215]
- French National Agency of Research [ANR-08-MNP-012]
- France-Parkinson Association
- French program Investissements d'avenir funding [ANR-10-IAIHU-06]
- Assistance Publique - Hopitaux de Paris (PHRC) [AOR-08010]
- Landspitali University Hospital Research Fund
- Icelandic Research Council
- European Community [PIAP-GA-2008-230596]
- Wellcome Trust [083948/Z/07/Z, 076113, 085475, 090355]
- Medical Research Council [G0700943, G1100643, G0501542]
- Wellcome Trust disease centre [WT089698/Z/09/Z]
- Parkinson's UK [8047, J-0804]
- Department of Health's National Institute for Health Research Biomedical Research Centres funding
- Wellcome Trust/Medical Research Council Joint Call in Neurodegeneration award [WT089698]
- Tracking Parkinson's - Parkinson's UK - Glasgow University
- National Institute for Health Research (NIHR) DeNDRoN network
- NIHR Newcastle Biomedical Research Unit based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University
- NIHRBiomedical Research Centre in Cambridge
- Parkinson's UK
- Paul Hamlyn Foundation
- Neurosciences Foundation
- Dystonia Society
- Michael's Movers
- Medical Research Council UK
- Ipsen Fund
- Motor Neuron Disease Association
- Welsh Assembly Government
- Cancer Research UK [19167, 10589] Funding Source: researchfish
- Medical Research Council [MR/L010305/1, G1100643, G0700943, G0501542, MR/L023784/2] Funding Source: researchfish
- Parkinson's UK [K-1501] Funding Source: researchfish
- MRC [G0700943, G0701075, G0501542, MR/L023784/2, G1100643] Funding Source: UKRI
A shared genetic susceptibility between cutaneous malignant melanoma (CMM) and Parkinson's disease (PD) has been suggested. We investigated this by assessing the contribution of rare variants in genes involved in CMM to PD risk. We studied rare variation across 29 CMM risk genes using high-quality genotype data in 6875 PD cases and 6065 controls and sought to replicate findings using whole-exome sequencing data from a second independent cohort totaling 1255 PD cases and 473 controls. No statistically significant enrichment of rare variants across all genes, per gene, or for any individual variant was detected in either cohort. There were nonsignificant trends toward different carrier frequencies between PD cases and controls, under different inheritance models, in the following CMM risk genes: BAP1, DCC, ERBB4, KIT, MAPK2, MITF, PTEN, and TP53. The very rare TYR p.V275F variant, which is a pathogenic allele for recessive albinism, was more common in PD cases than controls in 3 independent cohorts. Tyrosinase, encoded by TYR, is the rate-limiting enzyme for the production of neuromelanin, and has a role in the production of dopamine. These results suggest a possible role for another gene in the dopamine-biosynthetic pathway in susceptibility to neurodegenerative Parkinsonism, but further studies in larger PD cohorts are needed to accurately determine the role of these genes/variants in disease pathogenesis. (C) 2016 The Author(s). Published by Elsevier Inc.
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