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Multiple Sclerosis, Vol. 13, No. 4, 446-453 (2007)
DOI: 10.1177/13524585070130040201

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

A. Sidoti

Department of Biomorphology and Biotechnologies, University of Messina, 98100, Italy

C. Antognelli

Department of Experimental Medicine, University of Perugia, 06100, Italy

C. Rinaldi

Department of Biomorphology and Biotechnologies, University of Messina, 98100, Italy

R. D'Angelo

Department of Biomorphology and Biotechnologies, University of Messina, 98100, Italy

V. Dattola

Department of Neurosciences, Psychiatric and Anaesthesiological Sciences, University of Messina, 98100, Italy

P. Girlanda

Department of Neurosciences, Psychiatric and Anaesthesiological Sciences, University of Messina, 98100, Italy

V. Talesa

Department of Experimental Medicine, University of Perugia, 06100, Italy

A. Amato

Department of Biomorphology and Biotechnologies, University of Messina, 98100, Italy, aamato{at}unime.it

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. Multiple Sclerosis 2007; 13: 446-453. http://msj.sagepub.com

Key Words: glyoxalase I (GI) • lipid peroxidation • malondialdehyde (MDA) • methylglyoxal (MG) • multiple sclerosis (MS) • neurodegenerative diseases • paraoxonase (PON1) • polymorphisms


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