Evaluation of the Paraoxonases as Candidate Genes for Stroke

Ranade, Koustubh; Kirchgessner, Todd G.; Iakoubova, Olga A.; Devlin, James J.; Delmonte, Terrye A.; Vishnupad, Priya; Hui, Lester; Tsuchihashi, Zenta; Sacks, Frank M.; Sabatine, Marc S.; Braunwald, Eugene; White, Thomas J.; Shaw, Peter M.; Dracopoli, Nicholas C.

doi:10.1161/01.str.0000185703.88944.7d

Cited by 65 publications

(29 citation statements)

References 33 publications

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“…[49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66] Liu et al in 2013 conducted and published a systematic review and meta-analysis of 28 selected studies addressing these relationships. 21 They found that the R allele and the RR genotype of PON1 Q192R polymorphism correlated with a higher risk for ischemic stroke in the general population.…”

Section: Pon1 and Ischemic Strokementioning

confidence: 99%

Paraoxonase 1 in neurological disorders

Menini

Gugliucci

2013

Redox Report

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Paroxonase 1 displays multiple physiological activities that position it as a putative player in the pathogenesis of neurological disorders. Here we reviewed the literature focusing on the role of paraoxonase 1 (PON1) as a factor in the risk of stroke and the major neurodegenerative diseases. PON1 activity is reduced in stroke patients, which significantly correlates inversely with carotid and cerebral atherosclerosis. The presence of the R allele of the Q192R PON1 polymorphism seems to potentiate this risk for stroke. PON1 exerts peroxidase activities that may be important in neurodegenerative disorders associated with oxidative stress. PON1 is also a key detoxifier of organophosphates and organophosphate exposure has been linked to the development of neurological disorders in which acetylcholine plays a significant role. In Parkinson's disease most of the studies suggest no participation of either L55M or the Q192R polymorphisms in its pathogenesis. However, many studies suggest that the MM55 PON1 genotype is associated with a higher risk for Parkinson's disease in individuals exposed to organophosphates. In Alzheimer's disease most studies have failed to find any association between PON1 polymorphisms and the development of the disease. Some studies show that PON1 activity is decreased in patients with Alzheimer's disease or other dementias, suggesting a possible protective role of PON1. No links between PON1 polymorphisms or activity have been found in other neurodegenerative diseases such as multiple sclerosis and amyotrophic lateral sclerosis. PON1 is a potential player in the pathogenesis of several neurological disorders. More research is warranted to ascertain the precise pathogenic links and the prognostic value of its measurement in neurological patients.

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Section: Pon1 and Ischemic Strokementioning

confidence: 99%

Paraoxonase 1 in neurological disorders

Menini

Gugliucci

2013

Redox Report

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“…Studies assessing the significance of PON1 polymorphisms as risk factors of stroke in Asian populations have consistently shown that the Q192R [6, 7] and L55M polymorphisms influence the risk of this disease [8]. The R allele of the PON1 gene Q192R polymorphism was also found to be a risk of stroke in Caucasian stroke victims in North [9] and South [10] America. However, 2 studies performed on Caucasians in Europe did not show such a correlation [11, 12].…”

Section: Introductionmentioning

confidence: 99%

Paraoxonase 2 Gene C311S Polymorphism Is Associated with a Risk of Large Vessel Disease Stroke in a Polish Population

et al. 2007

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Background: Oxidative stress plays a role in atherosclerosis. Human paraoxonase (PON) gene products exhibit antioxidant properties. We studied the significance of the Q192R and M55L polymorphisms of the PON1 gene and the C311S polymorphism of the PON2 gene in different etiologies of ischemic stroke. Methods: One hundred and thirty-six patients with large vessel disease (LVD) stroke, 140 with small vessel disease stroke, 272 with cardioembolic stroke, and their age- and sex-matched controls were included. PON genotypes were evaluated by PCR-RFLP analyses. Results: The distribution of PON1 polymorphisms was similar in each stroke group and in the respective controls. Genotypes with the C allele of the PON2 gene C311S polymorphism were overrepresented in LVD stroke patients as compared with their controls, both in univariate and multivariate (dominant model: OR = 1.58, 95% CI: 1.006–2.48) analyses. Conclusion: The genotype with the C allele of the PON2 gene is a risk factor for LVD stroke in a Polish population.

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“…A positive association of Gln192Arg PON1 polymorphism and IS was described in the metaanalyses and in five case-control studies [177,178,184,185,188], but this association was negative in all other reports. Only two studies in Turkish populations obtained evidence for a positive association of Leu55Met PON1 polymorphism and IS [188,193], in contrast to 12 where no evidence for this association was found [28,30,[177][178][179]181,186,187,[190][191][192]194].…”

Section: Paraoxonase(pon)mentioning

confidence: 99%

“…Almost all research groups except one [192] agree that there is no significant association between IS and these polymorphisms [28,30,177,181,187,199] Four polymorphisms in the PON3 gene were examined in two studies on IS patients [181,187]. No evidence for an association was obtained.…”

Section: Paraoxonase(pon)mentioning

confidence: 99%