Further evidence for the association of CYP2D6*4 gene polymorphism with Parkinson’s disease: a case control study
Open accessAbstract
Genetic and environmental risk factors play an important role for the susceptibility to sporadic Parkinson’s disease (PD). It was hypothesized that a splice variant of the CYP2D6 gene ( CYP2D6*4 allele) is associated with PD because it alters the ability to metabolize toxins and in particular neurotoxins. CYP2D6 codes for the drug metabolizing enzyme debrisoquine 4-hydroxylase. The CYP2D6*4 variant results in an undetectable enzyme activity and consequently in a reduction in metabolism of some toxins. Some of agricultural chemicals have neurotoxic potential and CYP2D6 is involved in their detoxification. Thus, we conducted a case control study to investigate the association of the CYP2D6*4 with PD in a Pakistani subpopulation that is known to be exposed to high levels of some agricultural pesticides, insecticides and herbicides. We found a significantly higher allele and genotype frequency of the CYP2D6*4 variant in 174 sporadic PD patients when compared to 200 controls. In addition, there was a trend to an earlier age of PD onset and a tremor dominant phenotype in CYP2D6*4 variant carriers. Our data provide further evidence that a poor metabolizer status may increase the risk to develop PD especially in populations that are exposed to environmental toxins.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Individuals with reduced CYP2D6 activity due to mutated CYP2D6*4A genotype have a 2.5 times higher risk of PD than those with wild type, and this risk is higher in men.
“Moreover, a recent study found that individuals with reduced CYP2D6 activity due to the mutated CYP2D6 * 4A (allelic variants of CYP2D6) genotype had a 2.5 times higher risk of PD than those with wild type, which was higher in men [22].”
From Effect of Caffeine Consumption on the Risk for Neurological and Psychiatric Disorders: Sex Differences in Human (2020) · cites this paper as [22]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589 · see citing works
Molecular cloning: A laboratory manual
Deininger, P. L. (1990) · Analytical Biochemistry · doi:10.1016/0003-2697(90)90595-z · Cited by 84,684 · see citing works
Dauer, W., & Przedborski, S. (2003) · Neuron · doi:10.1016/s0896-6273(03)00568-3 · Cited by 5,469 · see citing works
Pharmacogenomics: Translating Functional Genomics into Rational Therapeutics
Evans, W. E., & Relling, M. V. (1999) · Science · doi:10.1126/science.286.5439.487 · Cited by 2,491 · see citing works
Variable expression of Parkinson's disease
Jankovic, J. J., McDermott, M., Carter, J., Gauthier, S. G., Goetz, C. G., Golbe, L. I., Huber, S. J., Koller, W. C., Olanow, C. W., Shoulson, I., et al. (1990) · Neurology · doi:10.1212/wnl.40.10.1529 · Cited by 1,285 · see citing works
Water pollution in Pakistan and its impact on public health — A review
Azizullah, A., Khattak, M. N. K., Richter, P. R., & Häder, D. (2010) · Environment International · doi:10.1016/j.envint.2010.10.007 · Cited by 891 · see citing works
Neurotoxicity of pesticides: a brief review
Lucio, G. C. (2007) · Frontiers in bioscience · doi:10.2741/2758 · Cited by 452 · see citing works
Pesticides and Parkinson’s Disease—Is There a Link?
Brown, T., Rumsby, P., Capleton, A., Rushton, L., & Levy, L. (2005) · Environmental Health Perspectives · doi:10.1289/ehp.8095 · Cited by 446 · see citing works
Sistonen, J., Sajantila, A., Lao, Ó., Corander, J., Barbujani, G., & Fuselli, S. (2007) · Pharmacogenetics and Genomics · doi:10.1097/01.fpc.0000239974.69464.f2 · Cited by 392 · see citing works
Parkinson's disease and brain levels of organochlorine pesticides
Fleming, L. E., Mann, J. B., Bean, J. A., Briggle, T. V., & Sanchez‐Ramos, J. (1994) · Annals of Neurology · doi:10.1002/ana.410360119 · Cited by 353 · see citing works
Pesticides exposure in Pakistan: A review
Tariq, M. I., Afzal, S., Hussain, I., & Sultana, N. (2007) · Environment International · doi:10.1016/j.envint.2007.07.012 · Cited by 280 · see citing works
ORGANOCHLORINE INSECTICIDES IN SUBSTANTIA NIGRA IN PARKINSON'S DISEASE
Corrigan, F. (2000) · Journal of Toxicology and Environmental Health · doi:10.1080/009841000156907 · Cited by 251 · see citing works
Pesticide/Environmental Exposures and Parkinson's Disease in East Texas
Dhillon, A. S., Tarbutton, G. L., Levin, J. L., Plotkin, G. M., Lowry, L. K., Nalbone, J. T., & Shepherd, S. (2008) · Journal of Agromedicine · doi:10.1080/10599240801986215 · Cited by 238 · see citing works
Pesticides and Risk of Parkinson Disease
Firestone, J. A., Smith‐Weller, T., Franklin, G. M., Swanson, P. D., Longstreth, W. T., Jr., & Checkoway, H. (2005) · Archives of Neurology · doi:10.1001/archneur.62.1.91 · Cited by 232 · see citing works
Progress in unraveling the genetic etiology of Parkinson disease in a genomic era
Verstraeten, A., Theuns, J., & Van Broeckhoven, C. (2015) · Trends in Genetics · doi:10.1016/j.tig.2015.01.004 · Cited by 226 · see citing works
CYP2D6 polymorphism, pesticide exposure, and Parkinson's disease
Elbaz, A., Lévecque, C., Clavel, J., Vidal, J., Richard, F., Amouyel, P., Alpérovitch, A., Chartier‐Harlin, M., & Tzourio, C. (2004) · Annals of Neurology · doi:10.1002/ana.20051 · Cited by 212 · see citing works
Dieldrin-Induced Neurotoxicity: Relevance to Parkinson's Disease Pathogenesis
Kanthasamy, A. G., Kitazawa, M., Kanthasamy, A., & Anantharam, V. (2004) · NeuroToxicology · doi:10.1016/j.neuro.2004.07.010 · Cited by 201 · see citing works
Cannon, J. R., & Greenamyre, J. T. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.06.025 · Cited by 191 · see citing works
Paraoxonase 1, Agricultural Organophosphate Exposure, and Parkinson Disease
Manthripragada, A. D., Costello, S., Cockburn, M., Bronstein, J. M., & Ritz, B. R. (2009) · Epidemiology · doi:10.1097/ede.0b013e3181c15ec6 · Cited by 169 · see citing works
Diazinon, chlorpyrifos and parathion are metabolised by multiple cytochromes P450 in human liver
Mutch, E., & Williams, F. M. (2006) · Toxicology · doi:10.1016/j.tox.2006.04.024 · Cited by 135 · see citing works
Sams, C., Mason, H. J., & Rawbone, R. G. (2000) · Toxicology Letters · doi:10.1016/s0378-4274(00)00221-6 · Cited by 134 · see citing works
Comparison of Two CYP2D6 Genotyping Methods and Assessment of Genotype-Phenotype Relationships
Chou, W.-H., Yan, F., Robbins‐Weilert, D., et al. (2003) · Clinical Chemistry · doi:10.1373/49.4.542 · Cited by 121 · see citing works
Isoquinoline derivatives as endogenous neurotoxins in the aetiology of Parkinson’s disease
McNaught, K. S. P., Carrupt, P., Altomare, C., et al. (1998) · Biochemical Pharmacology · doi:10.1016/s0006-2952(98)00142-7 · Cited by 118 · see citing works
Mann, A., Miksys, S. L., Gaedigk, A., Kish, S. J., Mash, D. C., & Tyndale, R. F. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.08.014 · Cited by 92 · see citing works
Soil Science: Agricultural and Environmental Prospectives
Sabir, M., Akhtar, J., & Hakeem, K. R. (2016) · Springer eBooks · doi:10.1007/978-3-319-34451-5 · Cited by 89 · see citing works
Adverse effects of pesticides residues on biochemical markers in pakistani tobacco farmers.
Khan, D. A., Bhatti, M. M., Khan, F. A., Naqvi, S. T. A., & Karam, A. (2008) · PubMed Central · Cited by 85 · see citing works
Ahad, K., Mohammad, A., Khan, H., Ahmad, I., & Hayat, Y. (2009) · Environmental Monitoring and Assessment · doi:10.1007/s10661-009-0995-5 · Cited by 77 · see citing works
Bajpai, P., Sangar, M. C., Singh, S., Tang, W., Bansal, S., Chowdhury, G., Cheng, Q., Fang, J.-K., Martin, M. V., Guengerich, F. P., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.402123 · Cited by 77 · see citing works
The endogenous substrates of brain CYP2D
Wang, X., Li, J., Dong, G., & Yue, J. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.12.025 · Cited by 73 · see citing works
Allele and genotype frequency of CYP2C19 in a Tamilian population
Adithan, C., Gérard, N., Vasu, S., et al. (2003) · British Journal of Clinical Pharmacology · doi:10.1046/j.1365-2125.2003.01883.x · Cited by 71 · see citing works
Use of In Vivo Animal Models to Assess Pharmacokinetic Drug-Drug Interactions
Tang, C., & Prueksaritanont, T. (2010) · Pharmaceutical Research · doi:10.1007/s11095-010-0157-z · Cited by 68 · see citing works
Monitoring health implications of pesticide exposure in factory workers in Pakistan
Khan, D. A., Hashmi, I., Mahjabeen, W., et al. (2009) · Environmental Monitoring and Assessment · doi:10.1007/s10661-009-1107-2 · Cited by 65 · see citing works
CYP2D6 Genetic Polymorphism in South Indian Populations
Naveen, A., Adithan, C., Soya, S. S., et al. (2006) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.29.1655 · Cited by 63 · see citing works
Association between the oxidative polymorphism and early onset of Parkinson's disease*
Agúndez, J. A. G., Jiménez‐Jiménez, F. J., Luengo, A., Bernal, M. L., Molina, J. A., Ayuso, L. L., Vázquez, A., Parra, J., Duarte, J., Coria, F., et al. (1995) · Clinical Pharmacology & Therapeutics · doi:10.1016/0009-9236(95)90154-x · Cited by 62 · see citing works
Do multiple cytochrome P450 isoforms contribute to parathion metabolism in man?
Mutch, E., Daly, A. K., Leathart, J. B. S., Blain, P. G., & Williams, F. M. (2003) · Archives of Toxicology · doi:10.1007/s00204-003-0452-0 · Cited by 48 · see citing works
Environmental-Genetic Interactions in the Pathogenesis of Parkinson's Disease
Tsuboi, Y. (2012) · Experimental Neurobiology · doi:10.5607/en.2012.21.3.123 · Cited by 37 · see citing works
The sparteine/debrisoquine (CYP2D6) oxidation polymorphism and the risk of Parkinson??s disease
Christensen, P. M., Gøtzsche, P. C., & sen, K. B. (1998) · Pharmacogenetics · doi:10.1097/00008571-199812000-00003 · Cited by 36 · see citing works
CYP2D6*4 Allele Polymorphism Increases the Risk of Parkinson’s Disease: Evidence from Meta-Analysis
Yu, L., Mo, C., Zeng, Z., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0084413 · Cited by 27 · see citing works
Akhmedova, S. N., Pushnova, E. A., Yakimovsky, A. F., et al. (1995) · Biochemical and Molecular Medicine · doi:10.1006/bmme.1995.1012 · Cited by 19 · see citing works
Parkinson’s Disease and CYP2D6 Polymorphism in Asian Populations: A Meta-Analysis
Persad, A. S., Stedeford, T. J., Tanaka, S., et al. (2003) · Neuroepidemiology · doi:10.1159/000072926 · Cited by 15 · see citing works
Source apportionment using reconstructed mass calculations
Siddique, N., & Waheed, S. (2013) · Journal of Environmental Science and Health Part A · doi:10.1080/10934529.2014.854687 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Jee, H. J., Lee, S. G., Bormate, K. J., & Jung, Y.-S. (2020) · Nutrients · doi:10.3390/nu12103080 · Cited by 111 · see citing works
“5 times higher risk of PD than those with wild type, which was higher in men [22].”
Background
- Authors
- Anwarullah, Aslam, M., Badshah, M., Abbasi, R., Sultan, A., Khan, K., Ahmad, N., & von Engelhardt, J.
- Affiliations
- German Center for Neurodegenerative Diseases (DE)
- Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad (PK)
- Institute of Biomedical and Genetic Engineering (PK)
- Quaid-i-Azam University (PK)
- University of Balochistan (PK)
- Venue
- Genes and Environment
- Published
- 2017-07-01
- Volume
- 39
- Issue
- 1
- Pages
- 18-18
- ISSN
- 1880-7046 (ISSN-L)
- 1880-7062
- PMC
- PMC5493842
- OpenAlex
- W2609069535
- Cited by
- 27
- References
- 41
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 8 · 2019: 1 · 2018: 1 · 2017: 1
- FWCI
- 3.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Genes and Environment (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Greater South Information System
- Funders
- german academic exchange service, bonn
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Keywords
- Parkinson's disease, CYP2D6*4, poor metabolizer phenotype, pesticide exposure, agrochemicals, neurotoxins, genetic susceptibility, age of onset, tremor-dominant phenotype, Pakistani population
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
