Abstract | INTRODUCTION: METHODS: This retrospective cohort study included patients with concurrent measurements of 6-TGN and BMI. The association between 6-TGN and clinical variables including BMI was estimated using a multivariable linear regression model. RESULTS: Of 132 observations, 77 [58%] had Crohn's disease and 55 [42%] ulcerative colitis. BMI, smoking, and TPMT levels were associated with 6-TGN levels in multivariable analysis. Every 5kg/m(2) increase in BMI was associated with an 8% decrease in 6-TGN (0.92; 95% confidence interval [CI] 0.87-0.98; p = 0.009). Smokers had higher 6-TGN levels in comparison with non-/ex-smokers [1.43; 95% CI 1.02-2.02; p = 0.041]. Patients with intermediate TPMT had higher 6-TGN compared to those with normal levels [2.13; 95% CI 1.62-2.80; p < 0.001]. Obese patients were more likely to have sub-therapeutic 6-TGN levels and a higher methyl mercaptopurine nucleotide [MMPN/TGN] ratio despite a similar dose of thiopurines. CONCLUSIONS: Active smoking and intermediate TPMT values were associated with higher 6-TGN levels but increasing BMI resulted in lower 6-TGN and higher MMPN levels. This may explain the worse outcome that has been reported previously in obese IBD subjects.
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Authors | Shi Sum Poon, Rebecca Asher, Richard Jackson, Andrew Kneebone, Paul Collins, Chris Probert, Martyn Dibb, Sreedhar Subramanian |
Journal | Journal of Crohn's & colitis
(J Crohns Colitis)
Vol. 9
Issue 8
Pg. 640-6
(Aug 2015)
ISSN: 1876-4479 [Electronic] England |
PMID | 25968584
(Publication Type: Evaluation Study, Journal Article)
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Copyright | Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected]. |
Chemical References |
- Biomarkers
- Guanine Nucleotides
- Immunosuppressive Agents
- Thionucleotides
- 6-thioguanylic acid
- Mercaptopurine
- Azathioprine
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Topics |
- Adult
- Azathioprine
(metabolism, therapeutic use)
- Biomarkers
(blood)
- Body Mass Index
- Colitis, Ulcerative
(blood, complications, drug therapy)
- Crohn Disease
(blood, complications, drug therapy)
- Drug Administration Schedule
- Female
- Guanine Nucleotides
(blood)
- Humans
- Immunosuppressive Agents
(metabolism, therapeutic use)
- Linear Models
- Male
- Mercaptopurine
(metabolism, therapeutic use)
- Middle Aged
- Obesity
(complications, diagnosis)
- Retrospective Studies
- Smoking
(adverse effects)
- Thionucleotides
(blood)
- Treatment Outcome
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