The C609T inborn polymorphism in NAD(P)H:quinone oxidoreductase 1 is associated with susceptibility to multiple sclerosis and affects the risk of development of the primary progressive form of the disease |
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Authors: | Stavropoulou Chrysa Zachaki Sophia Alexoudi Athanasia Chatzi Ioanna Georgakakos Vasileios N Terzoudi Georgia I Pantelias Gabriel E Karageorgiou Clementine E Sambani Constantina |
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Affiliation: | a Laboratory of Health Physics & Environmental Health, National Center for Scientific Research “Demokritos,” Athens 15310, Greeceb Neurology Department, General Hospital “G. Gennimatas,” Athens, Greecec Institute of Radioisotopes and Radiodiagnostic Products, National Center for Scientific Research “Demokritos,” Athens 15310, Greece |
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Abstract: | Oxidative stress plays a pivotal role in the pathogenesis of multiple sclerosis (MS). Inactivating polymorphisms of genes encoding detoxification enzymes, such as NAD(P)H:quinone oxidoreductase 1 (NQO1), could influence susceptibility to MS. To test this hypothesis we performed a case-control study in which we compared the distribution of NQO1 genotypes between 231 MS patients and 380 controls, using both PCR-RFLP and real-time PCR assays. Correlations with MS clinical subtype classification and gender were also evaluated. A significantly higher frequency of the homozygous (T/T) and heterozygous (C/T) NQO1 C609T variant genotypes was observed among MS patients compared to controls (P = 0.01), with MS patients showing a 1.5-fold increased risk of carrying at least one variant T allele (P = 0.009). Interestingly, patients belonging to the primary progressive subgroup exhibited a significantly higher incidence of the heterozygous C/T variant genotype, compared to the other forms of MS (P = 0.019). There was no correlation of the NQO1 polymorphism with gender. These results provide the first evidence for a pathogenetic role for the NQO1 C609T polymorphism in MS susceptibility and suggest a possible role for the NQO1 genetic background in the development of primary progressive MS. |
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Keywords: | ARE, antioxidant response element CNS, central nervous system EDSS, Expanded Disability Status System MS, multiple sclerosis NQO1, NAD(P)H:quinone oxidoreductase 1 PCR, polymerase chain reaction PP, primary progressive RFLP, restriction fragment length polymorphism ROS, reactive oxygen species RP, relapsing progressive RR, relapsing remitting SNP, single-nucleotide polymorphism SP, secondary progressive |
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