title: 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.
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 C(609)T 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 C(609)T polymorphism in MS susceptibility and suggest a possible role for the NQO1 genetic background in the development of primary progressive MS.
authors: Laboratory of Health Physics & Environmental Health, National Center for Scientific Research Demokritos, Athens 15310, Greece. cstavrop@ipta.demokritos.gr
authors: Chrysa
authors: C
authors: Stavropoulou
authors: Sophia
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authors: Zachaki
authors: Athanasia
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authors: Alexoudi
authors: Ioanna
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authors: Chatzi
authors: Vasileios N
authors: VN
authors: Georgakakos
authors: Georgia I
authors: GI
authors: Terzoudi
authors: Gabriel E
authors: GE
authors: Pantelias
authors: Clementine E
authors: CE
authors: Karageorgiou
authors: Constantina
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