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Table 12 Genes associated with the α-glutamyl cycle or trans-sulfation pathway

From: The potential role of the antioxidant and detoxification properties of glutathione in autism spectrum disorders: a systematic review and meta-analysis

Study Study Size Population Gene Polymorphism P value Finding
Glutathione-s- transferases      
GST-M1       
Buyske et al. 2006 [96] 172 controls (54 case parent trios) U.S. (non-Hispanic Caucasians) GST-M1 GST-M1*0 0.028 (Pearson's) 0.046(Likelihood ratio) Homozygotes with deletion at increased risk.
James et al. 2006 [47] 360 cases 205 controls U.S. (97% Caucasian) GST-M1 GST-M1*0 0.0671,2 Suggestive increase of null genotypes in cases.
Bowers et al. 2011 [94] 318 families (1,149 individuals) U.S. GST-M1 tag SNPs ns No association.
James et al. 2006 [47] As above As above GST-M1 + GST-M1*0: RFC 0.000141,2 This combination more frequent
    RFC 80A > G interaction   in cases. OR 3.78(95%CI 1.80, 7.95).
GST-P1       
Serajee et al. 2004 [97] 196 case parent trios U.S. GST-P1 rs947894 ns  
Bowers et al. 2011 [94] As above   GST-P1 tag SNPs ns  
GST-T1       
James et al. 2006 [47] As above As above GST-T1 GST-T1*0 ns2  
Glutathione peroxidase       
Ming et al. 2010 [95] 101 cases (results U.S GPx-1 GCG repeat   
  based on 68 trios    ALA5 ns  
  and 3 duos)    ALA6 0.017 Under-transmitted
     ALA7 ns  
Bowers et al. 2011 [94] As above As above GPx-1 tag SNPs ns  
ALAD   Single SNP analysis   
Rose et al. 2008 [50] 451 cases U.S. ALAD rs1800435 0.023 GC OR 1.65 (1.05-2.63)
  251 controls     0.6 CC OR 1.82 (0.14-95.73)
    Interaction analysis   
    ALAD rs1800435*GC   ALAD/RFC GG/AA reference
    RFC 80A > G combined 0.162 ALAD/RFC GC/AA OR 2.25 (0.72-7.06)
    genotype associated with 0.001 ALAD/RFC GCAG OR 3.98 (1.70-9.32)
    increased risk of autism. 0.237 ALAD/RFC GC/GG OR 1.79 (0.68-4.73)
Study Study Size Population Gene Polymorphism P value Finding
Other relevant genes   Single SNP analysis   
Bowers et al. 2011 [94] As above   CTH rs12737233 0.002 (0.30)3 CT OR 0.91 (0.65-1.28)
  (Validation study in 3327 individuals from independent     TT OR 4.83 (1.85-12.59)
  AGRE families)   GCLC rs761141 0.02 (0.10)3 CT OR 2.10 (1.20-3.69) TT OR 1.67 (0.91-3.09)
     rs524553 0.003 (0.08)3 CT OR 2.70 (1.47-4.98)
       TT OR 2.23 (1.16-4.28)
    DPP-1 tag SNPs ns  
    DPP-2 tag SNPs ns  
    DPP-3 tag SNPs ns  
    GGT-7 tag SNPs ns  
    GGT-5 tag SNPs ns  
    GGT-LA4 tag SNPs ns  
    GPx-2 tag SNPs ns  
    GPx-4 tag SNPs ns  
    GPx-7 tag SNPs ns  
    GST-A2 tag SNPs ns  
    GST-A3 tag SNPs ns  
    GST-A4 tag SNPs ns  
    GST-K1 tag SNPs ns  
    GST-M2 tag SNPs ns  
    GST-M3 tag SNPs ns  
    GST-M4 tag SNPs ns  
    GST-M5 tag SNPs ns  
    GST-O1 tag SNPs ns  
    GST-T2 tag SNPs ns  
    GST-Z1 tag SNPs ns  
    GST-CD tag SNPs ns  
    Interaction analysis   
    CTH rs12737233*C   OR 3.78 (95%CI 2.36-6.04)
    GLRX3 rs370834*A   
    GLRX rs17216887*G   
    allele combination associated   
    with increased risk of autism.   
  1. ns not significant GSTP1 Glutathione-S-transferase P1 GSTM1 Glutathione-S-transferase M1 RFC Reduced folate carrier SHMT Serine hydroxyl methyl transferase GPx-1 Glutathione peroxidase-1 ALA Poly-alanine repeat polymorphism CTH Cystathione gamma lyase GCLC γ-cysteine synthase, catalytic sub-unit GST-CD Glutathione-s-transferase, C terminal domain GGT-7 γ-glutamate transferase 7 GGT-5 γ-glutamate transferase 5 GGT-LA4 γ-glutamate transferase like activity 4 DPP Dipeptidase GLRX3 Glutaredoxin 3 GLRX Glutaredoxin SNP Single nucleotide polymorphism
  2. 1 Calculated by authors using EpiInfo version 6.0 Statcalc 2 Uncorrected 3P value from validation study in independent AGRE families