Gene-environment interactions in parkinsonism and Parkinson's disease: the Geoparkinson study

Dick, F. D.; de Palma, G.; Ahmadi, A.; Osborne, A.; Scott, N. W.; Prescott, G. J.; Bennett, J.; Semple, S.; Dick, S.; Mozzoni, P.; Haites, N.; Wettinger, S. Bezzina; Mutti, A.; Otelea, M.; Seaton, A.; Soderkvist, P.; Felice, A.
October 2007
Occupational & Environmental Medicine;Oct2007, Vol. 64 Issue 10, p673
Academic Journal
Objectives: To investigate associations of Parkinson's disease (PD) and parkirisonian syndromes with polymorphic genes that influence metabolism of either foreign chemical substances or dopamine and to seek evidence of gene-environment interaction effects that modify risk. Methods: A case-control study of 959 prevalent cases of parkinsonism (767 with PD) and 1989 controls across five European centres. Occupational hygienists estimated the average annual intensity of exposure to solvents, pesticides and metals, (iron, copper, manganese), blind to disease status. CYP2D6, PON1, GSTM 1, GSTT1, GSTM3, GSTP1, NQO1, CYPIB1, MAO-A, MAO-B, SOD 2, EPHX, DAT1, DRD2 and NAT2 were genotyped. Results were analysed using multiple logistic regression adjusting for key confounders. Results: There was a modest but significant association between MAO-A polymorphism in males and disease risk (G vs T, OR 1.30, 95% Cl 1.02 to 1.66, adjusted). The majority of gene-environment analyses did not show significant interaction effects. There were possible interaction effects between GSTM 1 null genotype and solvent exposure (which were stronger when limited to PD cases only). Conclusions: Many small studies have reported associations between genetic polymorphisms and PD. Fewer have examined gene-environment interactions. This large study was sufficiently powered to examine these aspects. GSTM1 null subjects heavily exposed to solvents appear to be at increased risk of PD. There was insufficient evidence that the other gene-environment combinations investigated modified disease risk, suggesting they contribute little to the burden of PD.


Related Articles

  • Fine-mapping and candidate gene investigation within the PARK10 locus. Haugarvoll, Kristoffer; Toft, Mathias; Skipper, Lisa; Heckman, Michael G.; Crook, Julia E.; Soto, Alexandra; Ross, Owen A.; Hulihan, Mary M.; Kachergus, Jennifer M.; Sando, Sigrid B.; White, Linda R.; Lynch, Timothy; Gibson, J. Mark; Uitti, Ryan J.; Wszolek, Zbigniew K.; Aasly, Jan O.; Farrer, Matthew J. // European Journal of Human Genetics;Mar2009, Vol. 17 Issue 3, p336 

    Herein, we investigate whether single-nucleotide polymorphisms (SNPs) across the PARK10 locus are associated with susceptibility to Parkinson's disease (PD) or age at onset (AAO) of disease. One hundred and eighty-eight SNPs were genotyped across the PARK10 locus in 180 PD patients and 180...

  • Population-based, Case-Control-Family Design to Investigate Genetic and Environmental Influences on Melanoma Risk. Cust, Anne E.; Schmid, Helen; Maskiell, Judith A.; Jetann, Jodie; Ferguson, Megan; Holland, Elizabeth A.; Agha-Hamilton, Chantelle; Jenkins, Mark A.; Kelly, John; Kefford, Richard F.; Giles, Graham G.; Armstrong, Bruce K.; Aitken, Joanne F.; Hopper, John L.; Mann, Graham J. // American Journal of Epidemiology;Dec2009, Vol. 170 Issue 12, p1541 

    Discovering and understanding genetic risk factors for melanoma and their interactions with phenotype, sun exposure, and other risk factors could lead to new strategies for melanoma control. This paper describes the Australian Melanoma Family Study, which uses a multicenter, population-based,...

  • Association between IFNA genotype and the risk of sarcoidosis. Akahoshi, Mitsuteru; Ishihara, Mami; Remus, Natascha; Uno, Kazuko; Miyake, Katsuhisa; Hirota, Tomomitsu; Nakashima, Kazuko; Matsuda, Akira; Kanda, Mizuo; Enomoto, Tadao; Ohno, Shigeaki; Nakashima, Hitoshi; Casanova, Jean-Laurent; Hopkin, Julian M.; Tamari, Mayumi; Mao, Xiao-Quan; Shirakawa, Taro // Human Genetics;Apr2004, Vol. 114 Issue 5, p503 

    Sarcoidosis is known to be a systemic granulomatous disorder characterized by a cell-mediated Th1-type inflammatory response. To identify a key genetic factor in the pathogenesis of sarcoidosis, we investigated single nucleotide polymorphisms within 10 candidate genes involved in type 1 immune...

  • Genotype-phenotype relationship of F7 R353Q polymorphism and plasma factor VII coagulant activity in Asian Indian families predisposed to coronary artery disease. SHANKER, JAYASHREE; PERUMAL, GANAPATHY; MAITRA, ARINDAM; RAO, VEENA S.; NATESHA, B. K.; JOHN, SHIBU; HEBBAGODI, SRIDHAR; KAKKAR, VIJAY V. // Journal of Genetics;Dec2009, Vol. 88 Issue 3, p291 

    Elevated factor VII (FVII) level is a risk factor for coronary artery disease (CAD). We investigated the role of R353Q polymorphism in the F7 gene in 139 Indian families with CAD, comprising of 222 affected subjects, 105 unaffected subjects and 126 affected sibling pairs. Plasma per cent FVIIc...

  • Apolipoprotein E polymorphism in Southern Iran: E4 allele in the lowest reported amounts. Masood Bazrgar; Mehran Karimi; Mohsen Fathzadeh; Sara Senemar; Farah Peiravian; Ashraf Shojaee; Mostafa Saadat // Molecular Biology Reports;Dec2008, Vol. 35 Issue 4, p495 

    Abstract   Background: Apolipoprotein E (apoE) with three major alleles E2, E3 and E4 is one of the critical genes in lipid metabolism. Common apoE alleles are in association with an increase in risk for central nervous and cardiovascular diseases such as Alzheimer’s disease,...

  • Genome-wide association study confirms extant PD risk loci among the Dutch. Simón-Sánchez, Javier; van Hilten, Jacobus J.; van de Warrenburg, Bart; Post, Bart; Berendse, Henk W.; Arepalli, Sampath; Hernandez, Dena G.; de Bie, Rob M. A.; Velseboer, Daan; Scheffer, Hans; Bloem, Bas; van Dijk, Karin D.; Rivadeneira, Fernando; Hofman, Albert; Uitterlinden, André G.; Rizzu, Patrizia; Bochdanovits, Zoltan; Singleton, Andrew B.; Heutink, Peter // European Journal of Human Genetics;Jun2011, Vol. 19 Issue 6, p655 

    In view of the population-specific heterogeneity in reported genetic risk factors for Parkinson's disease (PD), we conducted a genome-wide association study (GWAS) in a large sample of PD cases and controls from the Netherlands. After quality control (QC), a total of 514 799 SNPs genotyped in...

  • Genome-wide association study identifies three loci associated with melanoma risk. Bishop, D. Timothy; Demenais, Florence; Iles, Mark M.; Harland, Mark; Taylor, John C.; Corda, Eve; Randerson-Moor, Juliette; Aitken, Joanne F.; Avril, Marie-Francoise; Azizi, Esther; Bakker, Bert; Bianchi-Scarrà, Giovanna; Paillerets, Brigitte Bressac-de; Calista, Donato; Cannon-Albright, Lisa A.; Chin-A-Woeng, Thomas; Dębniak, Tadeusz; Galore-Haskel, Gilli; Ghiorzo, Paola; Gut, Ivo // Nature Genetics;Aug2009, Vol. 41 Issue 8, p920 

    We report a genome-wide association study of melanoma conducted by the GenoMEL consortium based on 317K tagging SNPs for 1,650 selected cases and 4,336 controls, with replication in an additional two cohorts (1,149 selected cases and 964 controls from GenoMEL, and a population-based case-control...

  • Lactase persistence-related genetic variant: population substructure and health outcomes. Smith, George Davey; Lawlor, Debbie A.; Timpson, Nic J.; Baban, Jamil; Kiessling, Matt; Day, Ian N. M.; Ebrahim, Shah // European Journal of Human Genetics;Mar2009, Vol. 17 Issue 3, p357 

    Lactase persistence is an autosomal-dominant trait that is common in European-derived populations. A basic tendency for lactase persistence to increase from the southeast to the northwest across European populations has been noted, but such trends within countries have not been extensively...

  • Association of TLR4 gene polymorphisms with sporadic Parkinson's disease in a Han Chinese population. Zhao, Jing; Han, Xun; Xue, Li; Zhu, Konghua; Liu, Hongxin; Xie, Anmu // Neurological Sciences;Sep2015, Vol. 36 Issue 9, p1659 

    Parkinson's disease (PD) is considered as a multifactorial disorder involving complex interactions between genetic and environmental factors, while previous studies point to a pivotal role of neuroinflammation in the pathophysiology of PD. As a member of pattern recognition receptors, TLR4 plays...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics