Genomic and Pharmacogenomic Biomarkers of Parkinson’s Disease
The relative role of genetic and environmental factors in the pathogenesis of Parkinson’s disease (PD) has been the matter of investigation and debate, especially in the last 30 years. The possible interaction between genetic and environmental factors led to a great number of
association studies between single nucleotide polymorphisms (SNPs) of many candidate genes and PD risk. In this study we summarized and critically reviewed the results of studies published on this issue, with especial reference to those reported in the last 5 years. Many studies provided conflicting
findings and, when positive associations were identified, associations were weak. Polymorphisms related with activation or detoxification of drugs and xenobiotics, such as CYP1A1, CYP1A2, CYP19A1, CYP1B1, CYP2C9, CYP2C19, CYP2E1, CYP2D6, NAT2, GSTM1, GSTM3, GSTO1, GSTP1, PON1, PON2, ABCB1
and ADH genes have not been demonstrated convincingly a definitive association with the risk of developing PD. Nor did polymorphisms in genes related to dopamine or serotonin DRD, DAT, TH, DDC, DBH, MAO, COMT, SLC6A4, MTR, MTHFR, oxidative stress NOQ1, NOQ2, mEPHX, HFE, GPX, CAT, mnSOD, HFE,
HO-1, HO-2, NFE2L2, KEAP1, inflammatory processes, ILs, TNF, ACT, NOS, HNMT, ABP1, HRHs, trophic and growth factors BDNF, FGF, or mitochondrial metabolism and function. In addition we analyzed other putative relations and genes associated with monogenic familial PD.Taking together the results
of candidate gene association studies and genome wide association studies, only some SNPs of the MAPT, SNCA, HLA and GBA genes seem to be the most likely associated with PD risk.
Keywords: Association studies; etiology; genetics; genome wide association studies; parkinson’s disease; pharmacogenetics; risk factors
Document Type: Research Article
Publication date: 01 February 2014
- Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:
In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts. - Editorial Board
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