Genetics, drugs and environmental factors in Parkinson's disease: a case-control study

Abstract

-A case-control study of Parkinson's disease (PD) was conducted in the city of Rio de Janeiro based on the assumption that neurotoxins with secondary parkinsonian action may be related to the development of Parkinson's disease. Ninety-two subjects with PD and 110 controls were queried through a questionnaire in order to investigate possible risk factors for the disease. The following factors were studied: herbicides/pesticides, exposure to chemicals, ingestion of drugs with secondary PD effects, rural life, water well source, family history, cranial trauma and cigarette smoking. Study of mentioned factors was achieved through univariate, stratified and multivariate analyses. Univariate and multivariate analyses demonstrated that PD was positively associated with family history (OR = 14.5; CI = 2.98 -91.38), with the use of drugs with secondary PD action (OR = 11.01; CI = 3.41 -39.41) and with exposure to chemical agents (OR = 5.87; CI = 1.48 -27.23). PD was found to be inversely associated with cigarette smoking (OR = 0.39; IC = 0.16 -0.95). Stratified analysis only confirmed family history and drug use, besides demonstrating that cigarette consumption could be a protection factor, when aforementioned factors were involved. This study might be a warning as to the cares that need to be taken regarding drug use and occupational exposure to chemical agents, as both types of substances present secondary PD action.KEY WORDS: Parkinson's disease, genetics, chemical agents, drugs, environmental factors. Genética, medicamentos e fatores do meio ambiente na doença de ParkinsonRESUMO -Um estudo caso-controle foi realizado na cidade do Rio de Janeiro, partindo-se do pressuposto de que neurotoxinas com ação parkinsoniana secundária poderiam facilitar a ocorrência da doença de Parkinson. Noventa e dois pacientes com doença de Parkinson e 110 controles foram avaliados através de questionário para a investigação de possíveis fatores de risco para a doença. Foram pesquisados os seguintes fatores: herbicidas e pesticidas, exposição a agentes químicos, uso de medicamentos com ação parkinsoniana secundária, vida rural, ingestão de água de poço, história familiar, passado de trauma central e consumo de cigarro. O estudo destes fatores foi realizado através das análises univariada, estratificada e multivariada. As análises univariada e multivariada demonstraram que a história familiar (RC = 14,5; IC = 2,38), o uso de medicamentos (RC = 11,01; IC = 3,41) e a exposição a agentes químicos (RC = 5,87; IC = 1,23) eram positivos como fatores de risco para a doença. Papel inverso foi ocupado pelo consumo de cigarros (RC = 0,39; IC = 0,16 -0,95). A análise estratificada confirmou apenas história familiar e medicamentos como fatores de risco, além de demonstrar que o consumo de cigarros poderia ser um fator de proteção, quando houve alguma participação destes mesmos fatores. Este estudo talvez possa alertar quanto aos cuidados que devem ser tomados na utilização de drogas e na atividade ocupacional com agentes químicos, quando estes...

Non-genetic factors associated with the risk of Parkinson�s disease in Iranian patients

“…The nicotine in cigarette smoke is believed to stimulate dopaminergic neurons, ameliorate PD symptoms and exert a neuroprotective effect (Wirdefeldt et al, 2011). Several studies have reported an inverse association between smoking and PD (Liou et al, 1997;Werneck and Alvarenga, 1999;Tan et al, 2003;Scott et al, 2005), whereas there are other studies, which do not suggest any notable association (Jiménez-Jiménez et al, 1992;Kuopio et al, 1999;Elbaz et al, 2000). Our data showed no association of smoking with PD in Iranian PD patients.…”

Traumatic Brain Injury in Adult Rats Causes Progressive Nigrostriatal Dopaminergic Cell Loss and Enhanced Vulnerability to the Pesticide Paraquat

“…Epidemiological studies have consistently implicated pesticide exposure as a risk factor in the development of PD, and experimental studies have demonstrated the ability of systemic administration of pesticides, in particular paraquat, to kill nigrostriatal dopaminergic neurons in rats and mice (Cicchetti et al, 2005;Costello et al, 2009;Fernagut et al, 2007;Hertzman et al, 1990;Liou et al, 1997;McCormack et al, 2002;Ossowska et al, 2005;Semchuk et al, 1992). In contrast, the role of TBI in the etiology of PD has been inconsistently documented (Bharucha et al, 1986;Bower et al, 2003;Goldman et al, 2006;Rugbjerg et al, 2008;Taylor et al, 1999;Werneck and Alvarenga, 1999) and, although it is known that TBI alters dopamine levels (Bales et al, 2009), and causes the appearance of degenerating neurons in the substantia nigra (Hicks et al, 1996), no previous research has demonstrated the ability of experimental TBI to induce a loss of nigrostriatal dopaminergic neurons similar to that observed in PD.…”

“…However, not all epidemiological studies have been able to demonstrate a statistically significant link between TBI and PD; some studies show a strong correlation (Bower et al, 2003;Goldman et al, 2006;Taylor et al, 1999), while others do not (Bharucha et al, 1986;Rugbjerg et al, 2008;Werneck and Alvarenga, 1999). These observations suggest that the link between TBI and PD may be contingent upon exposure to other risk factors, with TBI being one element sensitizing neurons to other risk factors, as suggested in the ''multiple hits'' hypothesis of PD (Sulzer, 2007).…”

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

“…One study reported an OR of 7.0 (p value <0.05) [289] and another an OR of 10.9 (95% CI 2.5-48.0) [301]. The remaining 19 case-control studies that analyzed results from pesticide exposure overall reported no association [131,136,137,141,142,144,145,[305][306][307][308][309][310][311][312][313][314][315][316][317].…”

“…Another study found an excess risk following exposure to chemical substances, such as methanol, toluene, cyanide, mercury or petroleum products (OR 5.87, 95% CI 1.48-27.23) [145]. The prospective study based on the Cancer Prevention II Nutrition Cohort in the US [330] reported no associations between risk of PD and exposure to asbestos, coal or stone dust, asphalt, diesel engine or gasoline exhaust, dyes, formaldehyde, textile dust, wood dust or radioactive material.…”