PMID- 25968584
OWN - NLM
STAT- MEDLINE
DCOM- 20160502
LR  - 20191210
IS  - 1876-4479 (Electronic)
IS  - 1873-9946 (Linking)
VI  - 9
IP  - 8
DP  - 2015 Aug
TI  - Body Mass Index and Smoking Affect Thioguanine Nucleotide Levels in Inflammatory 
      Bowel Disease.
PG  - 640-6
LID - 10.1093/ecco-jcc/jjv084 [doi]
AB  - INTRODUCTION: Optimal levels of the thiopurine metabolite, 6-thioguanine 
      nucleotides [6-TGN] correlate with remission of inflammatory bowel disease [IBD]. 
      Apart from variations in the thiopurine methyl transferase [TPMT] gene, little is 
      known about other predictors of 6-TGN levels. Obesity adversely affects response 
      to infliximab and adalimumab and clinical course in IBD, but little is known 
      about the interaction of thiopurines and obesity. We investigated the 
      relationship between body mass index [BMI] and 6-TGN levels and sought to examine 
      other predictors of 6-TGN levels. 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.
CI  - Copyright (c) 2015 European Crohn's and Colitis Organisation (ECCO). Published by 
      Oxford University Press. All rights reserved. For permissions, please email: 
      journals.permissions@oup.com.
FAU - Poon, Shi Sum
AU  - Poon SS
AD  - Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, 
      UK.
FAU - Asher, Rebecca
AU  - Asher R
AD  - Cancer Research UK Liverpool Cancer Trials Unit, Waterhouse Building, Liverpool, 
      UK.
FAU - Jackson, Richard
AU  - Jackson R
AD  - Cancer Research UK Liverpool Cancer Trials Unit, Waterhouse Building, Liverpool, 
      UK.
FAU - Kneebone, Andrew
AU  - Kneebone A
AD  - Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, 
      UK.
FAU - Collins, Paul
AU  - Collins P
AD  - Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, 
      UK.
FAU - Probert, Chris
AU  - Probert C
AD  - Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, 
      UK.
FAU - Dibb, Martyn
AU  - Dibb M
AD  - Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, 
      UK.
FAU - Subramanian, Sreedhar
AU  - Subramanian S
AD  - Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, 
      UK sreedhar.subramanian@rlbuht.nhs.uk.
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
DEP - 20150512
PL  - England
TA  - J Crohns Colitis
JT  - Journal of Crohn's & colitis
JID - 101318676
RN  - 0 (Biomarkers)
RN  - 0 (Guanine Nucleotides)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Thionucleotides)
RN  - 15867-02-4 (6-thioguanylic acid)
RN  - E7WED276I5 (Mercaptopurine)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - Adult
MH  - Azathioprine/metabolism/therapeutic use
MH  - Biomarkers/blood
MH  - *Body Mass Index
MH  - Colitis, Ulcerative/blood/complications/drug therapy
MH  - Crohn Disease/blood/complications/*drug therapy
MH  - Drug Administration Schedule
MH  - Female
MH  - Guanine Nucleotides/*blood
MH  - Humans
MH  - Immunosuppressive Agents/metabolism/*therapeutic use
MH  - Linear Models
MH  - Male
MH  - Mercaptopurine/metabolism/*therapeutic use
MH  - Middle Aged
MH  - Obesity/*complications/diagnosis
MH  - Retrospective Studies
MH  - Smoking/*adverse effects
MH  - Thionucleotides/*blood
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Crohn's disease
OT  - Inflammatory bowel disease
OT  - body mass index
OT  - smoking
OT  - thioguanine nucleotides
OT  - thiopurines
OT  - ulcerative colitis
EDAT- 2015/05/15 06:00
MHDA- 2016/05/03 06:00
CRDT- 2015/05/14 06:00
PHST- 2014/12/30 00:00 [received]
PHST- 2015/05/05 00:00 [accepted]
PHST- 2015/05/14 06:00 [entrez]
PHST- 2015/05/15 06:00 [pubmed]
PHST- 2016/05/03 06:00 [medline]
AID - jjv084 [pii]
AID - 10.1093/ecco-jcc/jjv084 [doi]
PST - ppublish
SO  - J Crohns Colitis. 2015 Aug;9(8):640-6. doi: 10.1093/ecco-jcc/jjv084. Epub 2015 
      May 12.