Paraoxonase 1 Met–Leu 54 polymorphism is associated with Parkinson’s disease

Akhmedova, S.N.; Yakimovsky, A.; Schwartz, E.I.

doi:10.1016/s0022-510x(01)00439-7

Cited by 92 publications

(68 citation statements)

References 17 publications

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“…Four studies investigating the association between PON1-55M/L polymorphism (Wang and Liu 2000;Akhmedova et al 2001;Carmine et al 2002;Kelada et al 2003) and PD and five studies investigating the association between PON1-192Q/R polymorphism and PD were identified (Kondo and Yamamoto 1998;Akhmedova et al 1999;Taylor et al2000;Wang and Liu 2000;Kelada et al 2003) (Table 1). Two studies (Wang and Liu 2000;Kelada et al 2003) investigated both the PON1-55M/L and PON1-192Q/R polymorphisms.…”

Section: Eligible Studiesmentioning

confidence: 99%

“…Two studies (Wang and Liu 2000;Kelada et al 2003) investigated both the PON1-55M/L and PON1-192Q/R polymorphisms. One study (Akhmedova et al 2001) presented results for both PON-55M/L and PON1-192Q/R; however, it was implied that the PON1-192 cases and controls were a subgroup of another eligible study (Akhmedova et al 1999) and therefore PON1-192 data of that study were not considered in the subsequent analysis.…”

Section: Eligible Studiesmentioning

confidence: 99%

“…Concerning the PON1-55M/L polymorphism, in three studies (Akhmedova et al 2001;Carmine et al 2002;Kelada et al 2003), the subjects were Caucasians, whilst in one study, the subjects were Asians (Wang and Liu 2000) (Table 1). In all four studies (Wang and Liu 2000;Akhmedova et al 2001;Carmine et al 2002;Kelada et al 2003), unrelated idiopathic PD patients were included; in one study (Carmine et al 2002) 28.9% of cases had affected relatives.…”

Section: Eligible Studiesmentioning

confidence: 99%

“…In all four studies (Wang and Liu 2000;Akhmedova et al 2001;Carmine et al 2002;Kelada et al 2003), unrelated idiopathic PD patients were included; in one study (Carmine et al 2002) 28.9% of cases had affected relatives. PD patients were diagnosed according to valid diagnostic criteria.…”

Section: Eligible Studiesmentioning

confidence: 99%

“…Some studies urged that the 55M variant of PON1 was a risk factor for developing PD (Carmine et al 2002;Akhmedova et al 2001;Kelada et al 2003), whilst other studies reported no genetic association between the PON1-55M/L polymorphism and PD (Wang and Liu 2000;Kelada et al 2003). Concerning the PON1-192Q/R polymorphism, there were studies that did not establish association between this polymorphism and susceptibility to PD (Akhmedova et al 1999;Taylor et al 2000;Wang and Liu 2000;Kelada et al 2003); however, one study urged that the 192R variant was a risk factor for developing PD (Kondo and Yamamoto 1998).…”

Section: Introductionmentioning

confidence: 99%

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Association of paraoxonase 1 gene polymorphisms with risk of Parkinson’s disease: a meta-analysis

2004

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Paraoxonase1 (PON1) gene polymorphisms were implicated as risk factors for Parkinson's disease (PD), but the results of case-control studies that investigated these associations were controversial. In order to provide an answer to these contradictory results, a metaanalysis of all available studies relating the PON1-55M/ L and PON1-192Q/R polymorphisms to the risk of developing PD was conducted. The racial descent of the populations in these studies was Caucasian and Asian. The meta-analysis revealed that there was an association of the PON1-55M allele and the risk of developing PD relative to the L allele: fixed effects pooled odds ratio (OR)=1.32 [95%CI (1.10-1.59)]. In addition, there was evidence of association for the genotypic contrast PON1-55MM+LM relative to PON1-55LL: fixed effects OR=1.50 [95%CI (1.16-1.95)]. There was no significant association between PON1-192Q/R alleles and risk of developing PD: OR=1.09 [95%CI (0.93-1.26)]. There was no evidence for an association between the genotypic contrasts of PON1-192 and development of PD. The heterogeneity between studies and the publication bias were not significant (P ‡0.10) in either polymorphism. Therefore, the pooled results of the meta-analysis supported that there was an association between PON1-55M/L polymorphism and PD and that PON1-192Q/R polymorphism was unlikely to be a major risk factor for susceptibility to PD.

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Section: Eligible Studiesmentioning

confidence: 99%

Section: Eligible Studiesmentioning

confidence: 99%

Section: Eligible Studiesmentioning

confidence: 99%

Section: Eligible Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of paraoxonase 1 gene polymorphisms with risk of Parkinson’s disease: a meta-analysis

2004

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Emerging roles for high‐density lipoproteins in neurodegenerative disorders

et al. 2019

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Lipoproteins are the complexes of different lipids and proteins, which are devoted to the transport and clearance of lipids or lipid‐related molecules in the circulation. Lipoproteins have been found to play a crucial role in brain function and may influence myelination process. Among lipoproteins, high‐density lipoproteins (HDLs) and their major protein component, apoA‐I, are directly involved in cholesterol efflux in the brain. It has been suggested that inadequate or dysfunctional brain HDLs may contribute to cerebrovascular dysfunctions, neurodegeneration, or neurovascular instability. HDL deficiency could also promote cognitive decline through impacting on atherosclerotic risk. The focus of this review is to discuss knowledge on HDL dysregulation in neurological disorders. A better understanding on how changes in cellular HDL and apolipoprotein homeostasis affect central nervous system function may provide promising novel avenues for the treatment of specific HDL‐related neurological disorders.

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Liver prenylated methylated protein methyl esterase is an organophosphate-sensitive enzyme

Lamango

2005

J. Biochem. Mol. Toxicol.

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Prenylation and subsequent methylation are essential modifications on a significant proportion of eucaryotic proteins. Proteins such as the G-gamma subunits of G-protein coupled receptors, nuclear lamins, and guanine nucleotide-binding proteins such as Ras are prenylated and undergo methylation. Prenylated methylated protein methyl esterase (PMPMEase) readily hydrolyses the prenylated protein methyl esters, thus making this step reversible and possibly regulatory. Benzoyl-glycyl-farnesyl-cysteine methyl ester (BzGFCM) was developed as a specific PMPMEase substrate and characterized by electron spray ionization mass spectrometry (ESI-MS) to be of the calculated molecular mass. Rat liver and brain PMPMEase hydrolyzed BzGFCM, forming benzoyl-glycyl-farnesyl-cysteine (BzGFC) in a time- and concentration-dependent manner. Both enzymes cleaved BzGFCM with K(m) values of 4.58 +/- 0.30 and 25.57 +/- 2.36 microM and V(max) values of 2.21 +/- 0.03 and 0.17 +/- 0.003 nmol/min/mg, respectively. The liver enzyme eluted from a gel-filtration column as a single peak of apparent size, 89 kDa. The brain enzyme eluted as two main peaks of 53 and 890 kDa. Organophosphorus pesticides (OPs), which are suspected to be involved in human disorders such as parkinsonism, neuronal, and retinal degeneration, inhibited the liver enzyme with IC(50) values from 4.77 muM for parathion to 0.04 microM for paraoxon, respectively. Only about 25% of the brain enzyme was inhibited by 0.5-1 mM solutions of mipafox, while 0.1 and 1 mM paraoxon inhibited over 50% and 95% of the enzyme, respectively. Paraoxon is thus about 2,250 times less potent against the brain than the liver PMPMEase. BzGFCM was not hydrolyzed by various cholinesterases, indicating its specificity for PMPMEase. Perturbations in prenylated protein metabolism might play a role in noncholinergic OPs-induced toxicity, since prenylated proteins play such important roles in cell signaling, proliferation, differentiation, and apoptosis.

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Paraoxonase 1 Met–Leu 54 polymorphism is associated with Parkinson’s disease

Cited by 92 publications

References 17 publications

Association of paraoxonase 1 gene polymorphisms with risk of Parkinson’s disease: a meta-analysis

Association of paraoxonase 1 gene polymorphisms with risk of Parkinson’s disease: a meta-analysis

Emerging roles for high‐density lipoproteins in neurodegenerative disorders

Liver prenylated methylated protein methyl esterase is an organophosphate-sensitive enzyme

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