PMID- 29191473 OWN - NLM STAT- MEDLINE DCOM- 20190412 LR - 20190412 IS - 1873-5126 (Electronic) IS - 1353-8020 (Print) IS - 1353-8020 (Linking) VI - 47 DP - 2018 Feb TI - Dopamine receptors and BDNF-haplotypes predict dyskinesia in Parkinson's disease. PG - 39-44 LID - S1353-8020(17)30805-2 [pii] LID - 10.1016/j.parkreldis.2017.11.339 [doi] AB - OBJECTIVE: Dyskinesia is a known side-effect of the treatment of Parkinson's Disease (PD). We examined the influence of haplotypes in three dopamine receptors (DRD1, DRD2 and DRD3) and the Brain Derived Neurotrophic Factor (BDNF) on dyskinesia. METHODS: Patient data were drawn from a population-based case-control study. We included 418 patients with confirmed diagnoses by movement disorder specialists, using levodopa and a minimum three years disease duration at the time of assessment. Applying Haploview and Phase, we created haploblocks for DRD1-3 and BDNF. Risk scores for DRD2 and DRD3 were generated. We calculated risk ratios using Poisson regression with robust error variance. RESULTS: There was no difference in dyskinesia prevalence among carriers of various haplotypes in DRD1. However, one haplotype in each DRD2 haploblocks was associated with a 29 to 50% increase in dyskinesia risk. For each unit increase in risk score, we observed a 16% increase in dyskinesia risk for DRD2 (95%CI: 1.05-1.29) and a 17% (95%CI: 0.99-1.40) increase for DRD3. The BDNF haploblock was not associated, but the minor allele of the rs6265 SNP was associated with dyskinesia (adjusted RR 1.31 (95%CI: 1.01-1.70)). CONCLUSION: Carriers of DRD2 risk haplotypes and possibly the BDNF variants rs6265 and DRD3 haplotypes, were at increased risk of dyskinesia, suggesting that these genes may be involved in dyskinesia related pathomechanisms. PD patients with these genetic variants might be prime candidates for treatments aiming to prevent or delay the onset of dyskinesia. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Kusters, Cynthia D J AU - Kusters CDJ AD - Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA. Electronic address: cynthiakusters@gmail.com. FAU - Paul, Kimberly C AU - Paul KC AD - Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA. FAU - Guella, Ilaria AU - Guella I AD - Department of Medical Genetics, Centre for Applied Neurogenetics, University of British Columbia, Vancouver, BC, Canada. FAU - Bronstein, Jeff M AU - Bronstein JM AD - Department of Neurology, David Geffen School of Medicine, Los Angeles, CA, USA. FAU - Sinsheimer, Janet S AU - Sinsheimer JS AD - Department of Biostatistics, UCLA Fielding School of Public Health, Los Angeles, CA, USA; Department of Human Genetics and Biomathematics, David Geffen School of Medicine, Los Angeles, CA, USA. FAU - Farrer, Matt J AU - Farrer MJ AD - Department of Medical Genetics, Centre for Applied Neurogenetics, University of British Columbia, Vancouver, BC, Canada. FAU - Ritz, Beate R AU - Ritz BR AD - Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA; Department of Neurology, David Geffen School of Medicine, Los Angeles, CA, USA; Department of Environmental Health, UCLA Fielding School of Public Health, Los Angeles, CA, USA. LA - eng GR - P30 ES007048/ES/NIEHS NIH HHS/United States GR - U54 ES012078/ES/NIEHS NIH HHS/United States GR - T32 HG002536/HG/NHGRI NIH HHS/United States GR - R01 ES010544/ES/NIEHS NIH HHS/United States GR - P50 NS038367/NS/NINDS NIH HHS/United States GR - P01 ES016732/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20171124 PL - England TA - Parkinsonism Relat Disord JT - Parkinsonism & related disorders JID - 9513583 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Receptors, Dopamine) RN - 46627O600J (Levodopa) SB - IM MH - Aged MH - Brain-Derived Neurotrophic Factor/*genetics MH - Case-Control Studies MH - Community Health Planning MH - Dyskinesia, Drug-Induced/etiology/*genetics MH - Female MH - Follow-Up Studies MH - Genetic Association Studies MH - Haplotypes MH - Humans MH - Levodopa/adverse effects MH - Male MH - Middle Aged MH - Parkinson Disease/drug therapy/*genetics MH - Receptors, Dopamine/*genetics MH - Retrospective Studies PMC - PMC5803389 MID - NIHMS923102 OTO - NOTNLM OT - DRD1-3 and BDNF genes OT - Dyskinesia OT - Haplotypes OT - Parkinson's disease COIS- Conflicts of Interest: None EDAT- 2017/12/02 06:00 MHDA- 2019/04/13 06:00 PMCR- 2019/02/01 CRDT- 2017/12/02 06:00 PHST- 2017/07/18 00:00 [received] PHST- 2017/10/14 00:00 [revised] PHST- 2017/11/21 00:00 [accepted] PHST- 2017/12/02 06:00 [pubmed] PHST- 2019/04/13 06:00 [medline] PHST- 2017/12/02 06:00 [entrez] PHST- 2019/02/01 00:00 [pmc-release] AID - S1353-8020(17)30805-2 [pii] AID - 10.1016/j.parkreldis.2017.11.339 [doi] PST - ppublish SO - Parkinsonism Relat Disord. 2018 Feb;47:39-44. doi: 10.1016/j.parkreldis.2017.11.339. Epub 2017 Nov 24.