Gysin et al. 10.1073/pnas.0706778104. |
Fig. 4. Functional relevance of the GCLC GAG TNR polymorphism in controls and patients of the Swiss sample. Note the following two aspects: (i) the functional effect of the GCLC GAG polymorphism was present in controls and thus independent of the disease; and (ii) some subjects with a low-risk genotype had a low GSH synthesis. It is possible that also other polymorphisms than the GCLC GAG TNR polymorphism can result in a lower GSH synthesis. The plots show GCL activity (t-BHQ) (A), GCLC protein expression (t-BHQ) (B), and GSH content (baseline) (C) of low-risk genotypes 7/7 and 7/9 (low) and high-risk genotypes 7/8, 8/8, 8/9, and 9/9 (high) separately for controls and patients.
Fig. 5. No evidence for a functional relevance of the GCLC GAG TNR polymorphism on GCLC gene expression. The plots show GCLC gene expression of 54 subjects with genotypes 7/7 and 7/9 and 15 subjects with genotypes 7/8, 8/8, 8/9, and 9/9. Each box describes 25% and 75% values, the horizontal line inside the box depicts median numbers, the whisker bars show the values in the 1.5 box lengths range, and the open circles depict outlier values.
Table 5. Distribution of GCLC GAG TNR genotypes in Swiss and Danish sample together
Genotypes | Controls | Patients | Odds ratio | 95% CI | P value | ||
N | % | N | % | ||||
7/7 | 149 | 39.3 | 107 | 27.6 | 0.59 | 0.43-0.80 | > 0.001 |
7/8 | 67 | 17.7 | 77 | 19.8 | 1.15 | 0.80-1.66 | 0.250 |
7/9 | 107 | 28.2 | 125 | 32.2 | 1.21 | 1.21-1.65 | 0.230 |
8/8 | 8 | 2.1 | 24 | 6.2 | 3.06 | 1.30-6.75 | 0.005 |
8/9 | 28 | 7.4 | 24 | 6.2 | 0.83 | 0.47-1.45 | 0.302 |
9/9 | 20 | 5.3 | 31 | 8.0 | 1.56 | 0.87-2.79 | 0.086 |
*Controls vs. Patients: (149, 67, 107, 8, 28, and 20 vs. 107, 77, 125, 24, 24, and 31) | 0.002 | ||||||
N
, number of genotypes in a group; %, percentage of genotypes in a group. Data are given together with odds ratio and 95% confidence interval (CI). P values were calculated using c2 test (two-tailed).*The frequency of genotypes between patients and controls was compared using c2 test (two-tailed) with a 2 ´ 6 contingency table (Controls and Patients ´ genotypes 7/7, 7/8, 7/9, 8/8, 8/9. and 9/9).
Table 6. Distribution of GCLC GAG TNR alleles in the New York sample and the control groups of the Danish and the Swiss sample
Allele | N | New York | Denmark | Swiss |
7 | 100 | 64 % | 61 % | 74 % |
8 | 331 | 15 % | 16 % | 3 % |
9 | 48 | 21 % | 23 % | 23 % |
N
, number of control subjects in the sample; %, percentage of the allele distribution. Controls in the New York and the Danish sample were randomly selected blood donors; controls in the Swiss sample were selected according to the DIGS.