Article

Glyoxalase I A111E, paraoxonase 1 Q192R and L55M polymorphisms: susceptibility factors of multiple sclerosis?

Department of Biomorphology and Biotechnologies, University of Messina, 98100, Italy.
Multiple Sclerosis (Impact Factor: 4.47). 06/2007; 13(4):446-53. DOI: 10.1177/13524585070130040201
Source: PubMed

ABSTRACT Multiple sclerosis (MS) is characterized by chronic inflammation and demyelination of the central nervous system (CNS). Accumulating data indicate that oxidative stress, leading to reactive oxygen species (ROS) production and lipid peroxidation, as well as elevated levels of advanced glycation end products (AGE) in CNS neurons, might play a pivotal role in the pathogenesis of a number of diseases with a neurodegenerative aspect, such as MS. Therefore, polymorphisms of genes encoding endogenous free-radical scavenging systems, such as paraoxonase 1 (PON1), and anti-glycation defences, such as glyoxalase I (GI), could influence susceptibility to MS. In the present study, we have undertaken a case-control study to investigate the possible association of GI A111E, PON1 Q192R and L55M polymorphisms with the risk of MS. The three polymorphisms were characterized in 209 patients with relapsing-remitting MS (RRMS) and in 213 healthy controls by PCR/RFLP methods using DNA from lymphocytes. We found that individuals with the GI/AE-EE genotypes and PON55/LM-MM genotypes had a significantly higher risk of MS compared with the other genotypes. The two polymorphisms appear to be common genetic traits that are associated with an increased risk for MS--the analysis of both, in each single case, may be a revealing predictable factor for MS risk.

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    ABSTRACT: Glyoxalase 1 is a scavenging enzyme of potent precursors in reactive oxygen species formation and is involved in the occurrence and progression of human malignancies. Glyoxalase I A111E polymorphism has been suggested to influence its enzymatic activity. The present study was aimed at investigating the association of this polymorphism with oxidative stress and its implications in prostate cancer progression or survival. The polymorphism was genotyped in human differently aggressive and invasive prostate cancer cell lines, in 571 prostate cancer or 588 benign prostatic hyperplasia patients, and 580 healthy subjects by Polymerase Chain Reaction/Restriction Fragment Length Polymorphism. Glyoxalase 1 activity, the pro-oxidant Glyoxalase 1-related Argpyrimidine and oxidative stress biomarkers were evaluated by biochemical analyses. Glyoxalase 1 polymorphism was associated with an increase in Glyoxalase 1-related pro-oxidant Argpyrimidine and oxidative stress levels and cancer progression. The mutant A allele conferred a modest risk of prostate cancer, a marked risk of prostate cancer progression and a lower survival time, compared to the wild C allele. The results of our exploratory study point out a significant role for Glyoxalase 1 in prostate cancer progression, providing an additional candidate for risk assessment in prostate cancer patients and an independent prognostic factor for survival. Finally, we provided evidence of the biological plausibility of Glyoxalase 1 polymorphism, either alone or in combination with other ones, all related to oxidative stress control that represents a key event in PCa development and progression.
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    ABSTRACT: Background and purpose: The aim of this study was to test the hypothesis that polymorphisms of the paraoxonase genes PON1 and PON2 may be associated with increased risk of developing multiple sclerosis (MS) in the Polish population. Material and methods: We studied the significance of the PON gene polymorphisms C311S, A162G, Q192R and L55M in 221 patients (including 145 women) with MS and in 661 healthy controls. In the MS population, mean Expanded Disability Status Scale score was 2.92, mean age was 36.8 years, and mean disease duration was 7.7 years. PON ge-notyping was determined using polymerase chain reaction and restriction enzyme digestion. Results: According to our results, the PON1 and PON2 genotypes distribution did not differ between the MS patients and the controls. Conclusions: The polymorphisms of the PON genes studied are not related to increased risk of MS in the Polish population.
    Neurologia i neurochirurgia polska 01/2013; 47(1):49-52. · 0.49 Impact Factor
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