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. Author manuscript; available in PMC: 2016 Oct 1.
Published in final edited form as: Nat Genet. 2016 Feb 15;48(4):367–373. doi: 10.1038/ng.3508

Figure 4. NUDT15 variants and MP metabolism in children during ALL therapy.

Figure 4

DNA-TG levels were analyzed in Singaporean (A and C) and Japanese (B and D) cohorts. Sixty-three and 44 samples were successfully measured from 32 cases with wildtype TPMT in Singapore and Japanese cohorts, respectively. An average DNA-TG level was estimated for each patient. The associations between MP dosage and DNA-TG were evaluated by two-sided Spearman rank test (A and B). DNA-TG level was normalized based on actual MP dosage (the average of 14 days) prior to metabolite measurements and then correlated with NUDT15 diplotype (as normal, intermediate, or low NUDT15 activity) using a linear regression model (two-sided, C and D). Similar association analyses were also performed to evaluate the difference in normalized DNA-TG between normal and intermediate NUDT15 groups (P = 0.14 and 0.039 for Panels C and D, respectively). Meta-analysis combining test statistics from two cohorts indicated consistent association of NUDT15 diplotype with normalized DNA-TG (P = 2.2 × 10−8), without significant heterogeneity across cohorts (P = 0.63). Each box includes data between 25th and 75th percentiles, with horizontal line indicating median.