Left: patients homozygous for the DRD3 ser allele;

right:

Left: patients homozygous for the DRD3 ser allele;

right: carriers of the DRD3 gly Gemcitabine synthesis allele (hétérozygotes … Brefeldin A clinical Another gene-gene interaction reported in relation to TD involved DRD3 and cytochrome P450 1A2 (CYP1A2). Both genes had been found to be independently associated with schizophrenia.19 Basile et al19 further found that, those patients who exhibited the risk genotype Inhibitors,research,lifescience,medical at, both DRD3 (gly9/gly9) and at CYP1A2 (CC) had the most, severe TD, whereas those who had only one risk genotype (gly9/gly9 or CC) demonstrated intermediate severity of TD. Those patients who did not, have any risk genotypes at either locus demonstrated the lowest mean TD severity scores on the AIM’S scale (P<0.00007). A more recent Inhibitors,research,lifescience,medical report of gene-gene interaction conferring susceptibility to TD concerns the functional ala9val polymorphism in exon 2 of the magnesium superoxide dismutase gene (MnSOD). MnSOD is one of three isoforms of superoxide dismutase (SOD) that are important, as antioxidants in protecting cells from the deleterious effects of free radicals. The ala9 variant, is associated with less efficient, functional activity of the enzyme. Hori et al20 found a small but, significant increase in the wild type val allele in Japanese schizophrenia patients with TD, suggesting that

the ala allele may be protective against, free radical damage in TD. This finding was not, replicated by Zhang et al21 in Inhibitors,research,lifescience,medical Chinese schizophrenia patients with TD. However, in a subsequent report Zhang et al22 found that the val-val Inhibitors,research,lifescience,medical genotype was in fact associated with TD, but. only in those patients who were carriers of the gly allele of the DRD3 scr9gly polymorphism. We examined

association of the ala9val polymorphism of MnSOD with TD in Israeli schizophrenia patients and also tested for an interaction Inhibitors,research,lifescience,medical between this polymorphism and the DRD3 ser9gly polymorphism (Segman et al, unpublished data). Patients were grouped according to whether they were carriers of the ala allele of MnSOD, the gly allele of DRD3, both, or neither. This grouping takes into account an effect, of DRD3 gly to increase susceptibility and a protective effect, of MnSOD ala and anticipates GSK-3 that patients carrying DRD3 gly and lacking MnSOD-ala will be most, susceptible to TD and will have the most severe abnormal involuntary movements. This is indeed the case. The MnSOD-val DRD3-gly genotype combination was the most, frequent, among patients with TD (64%) and the MnSOD-ala DRD3-ser genotype (24%) was the least frequent. Among patients without, TD the pattern was reversed. The most frequent genotype combination was Mn.SOD-ala\ DRD3-ser (76%) and the least frequent, combination was MnSOD-val DRD3-gly (38%, X 2=10.5, df=3, P=0.01). Table I shows that patients with the MnSOD-val\ DRD3-gly genotype combination have the highest, AIM’S total scores and patients with the MnSOD-ala DRD3-ser genotype combination have the lowest (F=6.16; df=3, 102; P=0.

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