title: Combined GSTP1 and NQO1 germline polymorphisms in the susceptibility to Multiple Sclerosis.
abstract: Germline polymorphisms of detoxification genes could influence susceptibility to Multiple Sclerosis (MS). Glutathione-S-transferases (GSTs) and
  quinone oxidoreductase 1 (NQO1) are detoxifying enzymes involved in biotransformation of metabolites preventing cells from oxidative damage. In order to evaluate the possible contribution of the A313G GSTP1 inactivating polymorphism, alone and in combination with the C609T NQO1 genetic variant in MS susceptibility, we performed a case-control study consisting of 254 MS patients and 370 healthy donors. Genotypes were investigated using a new Real-Time PCR and PCR-RFLP assays. The GSTP1 polymorphism was evaluated in relation to patients' characteristics (clinical subtypes, age and gender) and the NQO1 gene status. GSTP1 genotype distribution was similar between cases and controls. Higher frequency of GSTP1 heterozygotes was observed in patients with relapsing remitting disease (RRMS) (p = 0.019), especially in those presenting a benign form (EDSS ≤ 2 after 10-15 years from the disease onset). Interestingly, genotype distribution analysis of combined GSTP1 and NQO1 polymorphisms revealed significantly higher frequency of GSTP1 heterozygous (A/G) and NQO1 variant genotypes (C/T and T/T) in patients as compared to the controls (p = 0.031). The increased incidence of combined GSTP1 and NQO1 variant genotypes in MS patients may suggest that defective function of detoxification enzymes might be an important determinant of susceptibility and clinical manifestation of the disease. Moreover, the results suggest a possible role for the GSTP1 heterozygous background in the development of RRMS.
authors.affiliation: 1Department of Neurology, General Hospital "G. Gennimatas", Athens, Greece.
authors.forename: Athanasia
authors.initials: A
authors.lastname: Alexoudi
authors.forename: Sophia
authors.initials: S
authors.lastname: Zachaki
authors.forename: Chrysa
authors.initials: C
authors.lastname: Stavropoulou
authors.forename: Ioanna
authors.initials: I
authors.lastname: Chatzi
authors.forename: Daphne
authors.initials: D
authors.lastname: Koumbi
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Stavropoulou
authors.forename: Panagoula
authors.initials: P
authors.lastname: Kollia
authors.forename: Clementine E
authors.initials: CE
authors.lastname: Karageorgiou
authors.forename: Constantina
authors.initials: C
authors.lastname: Sambani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004185:Disability Evaluation; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
chemical_list: D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi
keywords: GSTP1; Multiple Sclerosis (MS); NQO1; genetic susceptibility; germline polymorphism; oxidative stress (OS)