Interaction between GSTM1-null and CYP2D6-deficient alleles in the pathogenesis of Parkinson's disease.
The present study was conducted to examine the interaction between cytochrome p450 2D6: CYP2D6 (phase I) poor metabolizer (PM) and glutathione S-transferase M1: GSTM1 (phase II) null genotypes, among 103 unrelated French Parkinson's disease (PD) patients. Both genes are involved in the biotransformation process, and the main objective of that work is to assess synergic effect between CYP2D6 PM and GSTM1 null genotypes in PD patients. Patients with both GSTM1 null genotype and poor metabolizer CYP2D6 have shown a strong dependency of multiplicative interaction (9.50; P = 0.016); this have also been observed when combining GSTM1 null with CYP2D6*4 deficient alleles, but were at the limit of significance (2.18; P = 0.076). Such a combination of polymorphic peculiarities in studied metabolic genes might represent additional risk factor for development of sporadic PD.
Santt
O
O
Center of Molecular Neurogenetics, Paris, France.
Baranova
H
H
Albuisson
E
E
Bignon
Y-J
YJ
Lucotte
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015139:Blotting, Southern / Q000379:methods; D016022:Case-Control Studies; D019389:Cytochrome P-450 CYP2D6 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010300:Parkinson Disease / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length
D019389:Cytochrome P-450 CYP2D6; D005982:Glutathione Transferase