Paraoxonase‐1 Q192R polymorphism and risk of sporadic amyotrophic lateral sclerosis

Slowik, A; Tomik, Barbara; Partyka, Dorota; Turaj, Wojciech; Pera, Joanna; Dziedzic, Tomasz; Szermer, Paweł; Figlewicz, D. A.; Szczudlik, Andrzej

doi:10.1111/j.1399-0004.2006.00590.x

Cited by 11 publications

(9 citation statements)

References 7 publications

(7 reference statements)

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“…), in some cases in interaction with pesticide exposure, thus supporting the hypothesis that environmental toxicity in a susceptible host may precipitate such disorders [62][63][64][65]. ), in some cases in interaction with pesticide exposure, thus supporting the hypothesis that environmental toxicity in a susceptible host may precipitate such disorders [62][63][64][65].…”

Section: Position -108supporting

confidence: 56%

Paraoxonase-1 (PON1) as a Predictor of Biochemical Outcomes in Farmers

López¹,

Pena²,

Serrano³

et al. 2007

CEI

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Initially characterized for its ability to hydrolyze organophosphorus (OP) compounds, Paraoxonase-1 (PON1) has been reported to play an important role in modulating the toxicity of some of these agents, which are "in vitro" substrates for this enzyme. The PON1 polymorphism at position 192 confers different enzyme levels and catalytic activity in a substrate-dependent manner, which has been related to the differential sensitivity of individuals to the toxic effects of OPs, supporting a role for the enzyme as a susceptibility biomarker. Several epidemiologic studies have examined the involvement of PON1 in xenobiotic susceptibility in different scenarios, including occupational exposure to pesticides. The major results of our studies performed in plastic greenhouses workers from Southeast Spain are presented herein. Briefly, PON1 is not only an individual marker of susceptibility, but also a biological indicator of exposure to pesticides, since workers spraying these agents, mainly OPs, showed decreased enzyme levels. On the other hand, carriers of the PON1 192R allele had lower levels of erythrocyte cholinesterase, a lower risk of presenting pesticide-related symptomatology, and less risk of reporting a previous episode of pesticide poisoning. Regarding enzymes involved in oxidative stress, carriers of the PON1 R allele had higher glutathione reductase and lower catalase activities. Intriguingly, PON1 R allele was found to be an independent predictor of higher aspartate aminotransferase and lower amino-oxidase and creatine kinase activities in serum. These findings deserve further attention as they highlight the important role of individual biomarkers of susceptibility on pesticideinduced biochemical changes in target organs that may precede the appearance of clinical changes.

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Section: Position -108supporting

confidence: 56%

Paraoxonase-1 (PON1) as a Predictor of Biochemical Outcomes in Farmers

López¹,

Pena²,

Serrano³

et al. 2007

CEI

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“…Recently an association between paraoxonase-1 Q192R polymorphism and risk of sporadic ALS has been suggested, probably due to the slower detossification capacity of environmental chemicals such as organophpsphate insecticides and pesticides of the RR genotype carriers [29].…”

Section: Introductionmentioning

confidence: 99%

Geographic distribution of amyotrophic lateral sclerosis through motor neuron disease mortality data

Uccelli

Binazzi²,

Altavista

et al. 2007

Eur J Epidemiol

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Amyotrophic lateral sclerosis (ALS) is a rare and devastating neurological disorder of the adult age with a prognosis of about 2-3 years from the onset of the disease. No clear cause has been identified but it seems to be a multifactorial disease with genetic and environmental components involved. Increments of mortality rates were observed since 1980 both in Italy and in many other countries. The objective of the present study is to describe the distribution of ALS mortality in Italy in the period 1980-2001 detecting single municipalities or clusters with high mortality levels for motor neuron disease (MND). ALS represents the main part (85%) of the MND group which is globally identified by the IX ICD (International Classification of Diseases and Causes of Death) 335.2 code. Death numbers and standardized mortality ratios (SMR) for MND were calculated for all Italian municipalities through the ENEA mortality database system (data source: National Institute of Statistics-ISTAT), using national mortality rates as reference. Subsequently, in order to detect municipal clusters, spatial analysis was performed. Out of the 8,099 Italian municipalities, 132 where characterized by SMR values higher than expected. Moreover 16 clusters with significant high relative risk values (RR) were identified, 12 out of them including only a single municipality. Only 22 of the municipalities with high SMR were included in the clusters. In conclusion, the two different epidemiological methodologies demonstrated to be widely complementary in detecting the geographical distribution of the disease in terms of risk for populations. A first selection of the priority areas where analytical studies should be carried on, in order to identify risk factors associated to ALS, is tentatively suggested.

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“…2, p. 4299); moreover, the ALS excess is shown by not one but three independent studies (3-5) (including two in the supporting information). Although rarity of ALS reduces power for risk factor identification, mounting evidence supports a role for AChEi-relevant exposures (pesticides, paraoxonase genotypes regulating organophosphate detoxification) in sporadic ALS (6)(7)(8). While ALS remains rare and not a dominant contributor to neurological deaths, a significant ALS excess is still important.…”

Section: Reply To Blazer Et Al: Flawed Challenges To ''Acetylcholinementioning

confidence: 99%

Reply to Blazer et al. : Flawed challenges to “Acetylcholinesterase inhibitors and Gulf War illnesses”

Golomb¹

2008

Proc. Natl. Acad. Sci. U.S.A.

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Paraoxonase‐1 Q192R polymorphism and risk of sporadic amyotrophic lateral sclerosis

Cited by 11 publications

References 7 publications

Paraoxonase-1 (PON1) as a Predictor of Biochemical Outcomes in Farmers

Paraoxonase-1 (PON1) as a Predictor of Biochemical Outcomes in Farmers

Geographic distribution of amyotrophic lateral sclerosis through motor neuron disease mortality data

Reply to Blazer et al. : Flawed challenges to “Acetylcholinesterase inhibitors and Gulf War illnesses”

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