Rare variants analysis of cutaneous malignant melanoma genes in Parkinson's disease

NEUROBIOLOGY OF AGING

卷:48

Article

Lubbe, S. J.¹  Escott-Price, V.²  Brice, A.³  Gasser, T.^4,5  Pittman, A. M.⁶  Bras, J.⁶  Hardy, J.⁶  Heutink, P.⁷  Wood, N. M.^6,8  Singleton, A. B.⁹  Grosset, D. G.¹⁰  Carroll, C. B.^11,12  Law, M. H.¹³  Demenais, F.^14,15  Iles, M. M.¹⁶  Bishop, D. T.¹⁶  Newton-Bishop, J.¹⁶  Williams, N. M.²  Morris, H. R.¹ 

[1] UCL Inst Neurol, Dept Clin Neurosci, London NW3 2PF, England

[2] Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci,Dept Psychol Med, Med Res Council,Ctr Neuropsychiat Genet & Genom, Cardiff, S Glam, Wales

[3] UPMC Univ Paris 06, UMR S 1127, Inst Cerveau & Moelle Epiniere, INSERM,U 1127,CNRS,UMR 7225,Sorbonne Univ,ICM, Paris, France

[4] Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany

[5] German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany

[6] UCL Inst Neurol, Dept Mol Neurosci, London, England

[7] Vrije Univ Amsterdam, Med Ctr, Sect Med Genom, Dept Clin Genet, Amsterdam, Netherlands

[8] UCL Genet Inst, London, England

[9] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

[10] Queen Elizabeth Univ Hosp, Inst Neurol Sci, Dept Neurol, Glasgow, Lanark, Scotland

[11] Univ Plymouth, Peninsula Sch Med, Plymouth, Devon, England

[12] Univ Plymouth, Peninsula Sch Dent, Plymouth, Devon, England

[13] QIMR Berghofer Med Res Inst, Stat Genet, Brisbane, Qld, Australia

[14] INSERM, UMR 946, Genet Variat & Human Dis Unit, Paris, France

[15] Univ Paris Diderot, Inst Univ Hematol, Paris, France

[16] Leeds Inst Canc & Pathol, Sect Epidemiol & Biostat, Leeds, W Yorkshire, England

关键词: Parkinson's;    Cutaneous malignant melanoma;    Shared genetic background;    Pigmentation;    Tyrosinase;   

DOI  :  10.1016/j.neurobiolaging.2016.07.013

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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