Table 3.
Metabolite accumulation within the thiopurine methyltransferase intermediate activity cohort; wild-type genotype and heterozygous genotype compared
| TPMT ≤10.5 units | Wild-type genotype | Heterozygous genotype | Median difference (95% CI) |
|---|---|---|---|
| TG patients | 35 | 33 | |
| TG-TGNs (pmol) | 2 360 (910–4 060) | 2 626 (174–6 730) | 246 (−214, 664), P = 0.29, NS |
| TPMT (units) | 9.9 (5.4–10.5) | 7.7 (5.2–10.5) | −1.7 (−2.4, −1.0), P < 0.0001 |
| MP patients | 44 | 63 | |
| TG-TGNs (pmol) | 366 (0–1 216) | 754 (132–2 228) | 369 (250, 502), P < 0.0001 |
| MeMPNs (pmol) | 8 590 (0–96 964) | 3 825 (60–38 386) | −4822 (−7278, −2518), P = 0.0001 |
| TPMT (units) | 9.7 (5.6–10.5) | 7.8 (2.8–10.5) | −1.4 (−2.0, −0.7), P < 0.0001 |
MeMPNs, methylmercaptopurine nucleotides; MP, mercaptopurine cohort; TG, thioguanine cohort; TGNs, thioguanine nucleotides; TPMT, thiopurine methyltransferase. TGN and MeMPN units are pmol/8 × 108 red blood cells. TPMT units are units ml−1 packed red blood cells. For the intermediate activity cohort (TG n = 68, MP n = 114) median TG derived TGNs = 2492 pmol, MP derived TGNs = 562 pmol, MeMPNs = 5542 pmol. TPMT genotypes were available for all 68 children on thioguanine but only for 107 of the 114 children on mercaptopurine. The analysis excludes TPMT deficient children. Values are given as median (range).