Marika Falla1, Alessio Di Fonzo2, Andrew Anthony Hicks3, Peter Paul Pramstaller4, Giovanni Fabbrini5. 1. Center for Mind/Brain Sciences, University of Trento, Rovereto, TN, Italy; Institute for Biomedicine, Eurac Research, Bolzano, Italy; Department of Neurology, General Hospital of Bolzano, Bolzano, Italy. Electronic address: marika.falla@unitn.it. 2. Movement Disorder Research Group, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico di Milano, Italy. 3. Institute for Biomedicine, Eurac Research, Bolzano, Italy. 4. Institute for Biomedicine, Eurac Research, Bolzano, Italy; Department of Neurology, General Hospital of Bolzano, Bolzano, Italy. 5. Department Human Neurosciences, Sapienza University of Rome, Italy; IRCCS Neuromed, Pozzilli, Italy.
Abstract
INTRODUCTION: Levodopa-induced dyskinesia frequently complicates long-term Parkinson's disease. More in-depth knowledge regarding the role of genetic factors in dyskinesia development may be important to identify parkinsonian patients who are more prone to developing dyskinesia and clarify the molecular mechanisms underlying this condition. For this reason, we systematically reviewed studies investigating genetic factors involved in dyskinesia. METHODS: A systematic search of genetic factors in Parkinson's disease dyskinesia was performed using the MEDLINE (through PubMed up to June 2019) and EMBASE databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A meta-analysis was conducted using a random effect model. RESULTS: The literature search retrieved 33 studies assessing genes and variants possibly associated with dyskinesia in Parkinson's disease. The studies were published between 1984 and 2019 and included a total of 27,092 subjects of different ethnicities. Overall, 37 genes were analyzed in the studies reviewed, of which 22 were possibly associated with dyskinesia. The studies reported a total of 158 variants, of which 94 were possibly related to dyskinesia. CONCLUSION: The studies reviewed demonstrated inconsistent results, possibly due to differences in screening methods and in the comparison of clinical data in a large variety of genetically- and ethnically-diverse populations. The meta-analysis failed to demonstrate any association between the rs6280 in the DRD3 gene, rs1799836 in the MAO-B, rs4680 in the COMT gene, rs34637584 in the LRRK2 gene and LID susceptibility. The role of genetic factors in LID susceptibility is still unclear and further studies are required.
INTRODUCTION: Levodopa-induced dyskinesia frequently complicates long-term Parkinson's disease. More in-depth knowledge regarding the role of genetic factors in dyskinesia development may be important to identify parkinsonian patients who are more prone to developing dyskinesia and clarify the molecular mechanisms underlying this condition. For this reason, we systematically reviewed studies investigating genetic factors involved in dyskinesia. METHODS: A systematic search of genetic factors in Parkinson's disease dyskinesia was performed using the MEDLINE (through PubMed up to June 2019) and EMBASE databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A meta-analysis was conducted using a random effect model. RESULTS: The literature search retrieved 33 studies assessing genes and variants possibly associated with dyskinesia in Parkinson's disease. The studies were published between 1984 and 2019 and included a total of 27,092 subjects of different ethnicities. Overall, 37 genes were analyzed in the studies reviewed, of which 22 were possibly associated with dyskinesia. The studies reported a total of 158 variants, of which 94 were possibly related to dyskinesia. CONCLUSION: The studies reviewed demonstrated inconsistent results, possibly due to differences in screening methods and in the comparison of clinical data in a large variety of genetically- and ethnically-diverse populations. The meta-analysis failed to demonstrate any association between the rs6280 in the DRD3 gene, rs1799836 in the MAO-B, rs4680 in the COMT gene, rs34637584 in the LRRK2 gene and LID susceptibility. The role of genetic factors in LID susceptibility is still unclear and further studies are required.
Authors: Jodi Maple-Grødem; Kimberly C Paul; Ingvild Dalen; Kathie J Ngo; Darice Wong; Angus D Macleod; Carl E Counsell; David Bäckström; Lars Forsgren; Ole-Bjørn Tysnes; Cynthia D J Kusters; Brent L Fogel; Jeff M Bronstein; Beate Ritz; Guido Alves Journal: J Parkinsons Dis Date: 2021 Impact factor: 5.568