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{
  "pmid": "28927418",
  "doi": "10.1186/s12920-017-0291-0",
  "abstract": "1. BMC Med Genomics. 2017 Sep 19;10(1):56. doi: 10.1186/s12920-017-0291-0.\n\nA systematic review and integrative approach to decode the common molecular link \nbetween levodopa response and Parkinson's disease.\n\nGuin D(1), Mishra MK(1)(2), Talwar P(1), Rawat C(1)(3), Kushwaha SS(4), Kukreti \nS(2), Kukreti R(5)(6).\n\nAuthor information:\n(1)Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative \nBiology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, \nNew Delhi, -110007, India.\n(2)Department of Chemistry, Nucleic Acids Research Lab, University of Delhi \n(North Campus), Delhi, India.\n(3)Academy of Scientific & Innovative Research (AcSIR), CSIR- Institute of \nGenomics and Integrative Biology (CSIR-IGIB) Campus, New Delhi, India.\n(4)Institute of Human Behaviour and Allied Sciences, Dilshad Garden, Delhi, \nIndia.\n(5)Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative \nBiology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, \nNew Delhi, -110007, India. ritus@igib.res.in.\n(6)Academy of Scientific & Innovative Research (AcSIR), CSIR- Institute of \nGenomics and Integrative Biology (CSIR-IGIB) Campus, New Delhi, India. \nritus@igib.res.in.\n\nBACKGROUND: PD is a progressive neurodegenerative disorder commonly treated by \nlevodopa. The findings from genetic studies on adverse effects (ADRs) and \nlevodopa efficacy are mostly inconclusive. Here, we aim to identify predictive \ngenetic biomarkers for levodopa response (LR) and determine common molecular \nlink with disease susceptibility. A systematic review for LR was conducted for \nADR, and drug efficacy, independently. All included articles were assessed for \nmethodological quality on 14 parameters. GWAS of PD were also reviewed. \nProtein-protein interaction (PPI) analysis using STRING and functional \nenrichment using WebGestalt was performed to explore the common link between LR \nand PD.\nRESULTS: From 37 candidate studies on levodopa toxicity, 18 genes were found \nassociated, of which, CAn STR 13, 14 (DRD2) was most significantly associated \nwith dyskinesia, followed by rs1801133 (MTHFR) with hyper-homocysteinemia, and \nrs474559 (HOMER1) with hallucination. Similarly, 8 studies on efficacy resulted \nin 4 genes in which rs28363170, rs3836790 (SLC6A3) and rs4680 (COMT), were \nsignificant. To establish the molecular connection between LR with PD, we \nidentified 35 genes significantly associated with PD. With 19 proteins \nassociated with LR and 35 with PD, two independent PPI networks were \nconstructed. Among the 67 nodes (263 edges) in LR, and 62 nodes (190 edges) in \nPD pathophysiology, UBC, SNCA, FYN, SRC, CAMK2A, and SLC6A3 were identified as \ncommon potential candidates.\nCONCLUSION: Our study revealed the genetically significant polymorphism \nconcerning the ADRs and levodopa efficacy. The six common genes may be used as \npredictive markers for therapy optimization and as putative drug target \ncandidates.\n\nDOI: 10.1186/s12920-017-0291-0\nPMCID: PMC5606117\nPMID: 28927418 [Indexed for MEDLINE]\n\nConflict of interest statement: ETHICS APPROVAL AND CONSENT TO PARTICIPATE: No \npatient samples were collected and analysed during this study. All GWAS data \nwere provided as summary statistics by the consortia acknowledged in this study \nhaving been collected in accordance with ethical regulations in the partner \ncountries and as defined in original research publications by such consortia. \nCONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors \ndeclare no potential conflict of interest. PUBLISHER’S NOTE: Springer Nature \nremains neutral with regard to jurisdictional claims in published maps and \ninstitutional affiliations.",
  "journal": "BMC Med Genomics",
  "year": 2017,
  "authors": "Guin D, Mishra MK, Talwar P, Rawat C, Kushwaha SS, Kukreti S, Kukreti R",
  "url": "https://pubmed.ncbi.nlm.nih.gov/28927418",
  "external_ids": {
    "doi": "10.1186/s12920-017-0291-0",
    "pmid": "28927418"
  },
  "citation_count": 1,
  "domain": "neurodegeneration"
}