Polymorphisms at the Paraoxonase 1 L55M and Q192R Loci Affect the Pathophysiology of Alzheimer’s Disease: Emphasis on the Cholinergic System and Beta-Amyloid Levels

Leduc, Valérie; Poirier, Judes

doi:10.1159/000113709

Cited by 29 publications

(32 citation statements)

References 10 publications

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“…The association of PON1 gene polymorphism and risk of certain diseases has been documented (Sidoti et al, 2007;Leduc and Poirier, 2008;Agrawal et al, 2009;Leduc et al, 2009). In addition, PON1 gene polymorphisms (Q192R, L55M) alter both the level and activity of the enzyme (Humbert et al, 1993;Garin et al, 1997;Mackness et al, 1998;Aviram et al, 2000).…”

Section: Discussionmentioning

confidence: 98%

Lack of association between paraoxonase-1 Q192R polymorphism and rheumatoid arthritis in southeast Iran

Hashemi¹,

Moazeni‐Roodi²,

Fazaeli³

et al. 2010

Genet. Mol. Res.

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ABSTRACT. Decreased paraoxonase-1 (PON1) activity has been associated with rheumatoid arthritis. There are two polymorphisms in serum PON1; one differs in the amino acid at position 192 (Q192R) and the other one differs at position 55 (L55M). We looked for a possible association between Q192R polymorphism and rheumatoid arthritis. The Q192R polymorphism in 88 rheumatoid arthritis patients and 78 healthy subjects was determined using tetra amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and PCRrestriction fragment length polymorphism (RFLP) methods. We found no significant differences between rheumatoid arthritis patients and control subjects regarding PON1 Q192R polymorphism. PON1 Q192R polymorphism was not found to be correlated with increased risk for rheumatoid arthritis in this Iranian population.

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Section: Discussionmentioning

confidence: 98%

Lack of association between paraoxonase-1 Q192R polymorphism and rheumatoid arthritis in southeast Iran

Hashemi¹,

Moazeni‐Roodi²,

Fazaeli³

et al. 2010

Genet. Mol. Res.

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“…97 Multiple studies have addressed the association between PON1 polymorphisms and AD. 91,[98][99][100][101][102][103][104][105] In a study with 756 AD subjects, the authors found no association between the two major PON1 polymorphisms and AD in African Americans or Caucasians. 91 The authors conclude that either these functional PON1 polymorphisms are not associated with AD, or that the relative risk is small.…”

Section: 70-73mentioning

confidence: 93%

“…[25][26][27]92,94 In a large study with an over 1000 cohort of clinical and autopsy-confirmed AD cases and age-matched, cognitively intact controls, multiple gender-specific effects of PON1 polymorphisms on AD pathogenesis were apparent. 101 The L55M…”

mentioning

confidence: 99%

“…Associations with betaamyloid levels, senile plaque accumulation and cholinesterase activity suggest an involvement of the PON1 gene in AD pathogenesis and responses to treatment. 101 Regarding the possible interference between common SNPs in PON1, a recent study suggests that PON1 common SNPs do not impact on treatment response to acethylcholinesterase inhibitors in patients with AD.…”

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confidence: 99%

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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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“…Patients who developed dementia were found to have a higher frequency of the 55M allele (91)(92). Although Helpecque et al reported that the -107T allele meant high risk of dementia (93), it was concluded in another study that this observation was a contradiction (94).…”

Section: Clinical Significancementioning

confidence: 96%

The Past and Present of Paraoxonase Enzyme: Its Role in the Cardiovascular System and Some Diseases

Aydın¹,

Şahin²,

Aydın³

et al. 2012

Journal of Medical Biochemistry

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Summary: Although paraoxonase is synthesized in many tissues including the heart, colon, kidneys, lungs, small intestines and brain, its major locus of synthesis is the liver. PON1 is in close association with apolipoproteins and protects LDL against oxidation. It was reported that PON1 quantities dropped to 40 times lower than normal in cardiovascular diseases and diseases like diabetes, ulcerative colitis, Crohn's disease, chronic renal failure, SLE, Behcet's disease, cancer, hepatitis B, obesity, metabolic syndrome, Alzheimer's and dementia. It is speculated that the concerning decline in serum PON1 amount results from single nucleotide polymorphism in the coding (Q192R, L55M) and promoter (T-108C) sites of the PON1 gene. Additionally, circulating amounts of PON1 are affected by vitamins, antioxidants, fatty acids, dietary factors, drugs, age and lifestyle. This collection attempts to review and examine the past and present studies of paraoxonase and its relation with the cardiovascular system and some relevant diseases.Keywords: paraoxonase, polymorphism, cardiovascular system diseases Kratak sadr`aj: Iako se paraoksonaza sinteti{e u mnogim tkivima, uklju~uju}i srce, debelo crevo, bubrege, plu}a, tanko crevo i mozak, glavno mesto njene sinteze je jetra. PON1 je blisko povezana sa apolipoproteinima i {titi LDL od oksidacije. Koli~ine PON1 ~ak 40 puta ni`e od normalnog nivoa zabele`ene su u kardiovaskularnim bolestima i oboljenjima kao {to su dijabetes, ulcerozni kolitis, Kronova bolest, hroni~na bubre`na insuficijencija, sistemski eritemski lupus, Beh~etov sindrom, kancer, hepatitis B, gojaznost, metaboli~ki sindrom, Alchajmerova bolest i demencija. Spekuli{e se da pomenuti pad nivoa PON1 u serumu poti~e od polimorfizma pojedina~nih nukleotida na kodnim (Q192R, L55M) i promoterskim (T-108C) podru~jima gena PON1. Pored toga, na koli~inu PON1 u cirkulaciji uti~u vita mini, antioksidansi, masne kiseline, faktori ishra ne, le kovi, godine i na~in `ivota. Ovaj pregled predstavlja poku{aj da se izlo`e i razmotre pro{le i sada{nje studije o paraoksonazi i njenom odnosu sa kardiovaskularnim sistemom i nekim relevantnim bolestima.

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Polymorphisms at the Paraoxonase 1 L55M and Q192R Loci Affect the Pathophysiology of Alzheimer’s Disease: Emphasis on the Cholinergic System and Beta-Amyloid Levels

Cited by 29 publications

References 10 publications

Lack of association between paraoxonase-1 Q192R polymorphism and rheumatoid arthritis in southeast Iran

Lack of association between paraoxonase-1 Q192R polymorphism and rheumatoid arthritis in southeast Iran

Paraoxonase 1 in neurological disorders

The Past and Present of Paraoxonase Enzyme: Its Role in the Cardiovascular System and Some Diseases

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