PMID- 11843038
OWN - NLM
STAT- MEDLINE
DCOM- 20020726
LR  - 20190814
IS  - 0036-5521 (Print)
IS  - 0036-5521 (Linking)
VI  - 37
IP  - 1
DP  - 2002 Jan
TI  - Hyperhomocysteinaemia, coagulation pathway activation and thrombophilia in 
      patients with inflammatory bowel disease.
PG  - 62-7
AB  - BACKGROUND: The 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C-->T 
      polymorphism encoding the thermolabile variant is, when present as homozygote 
      type (TT variant), a known genetic cause of mild hyperhomocysteinaemia (HHCY). 
      This polymorphism has been observed in increased numbers in patients with 
      inflammatory bowel disease (IBD). Coagulation and fibrinolysis are activated in 
      patients with active IBD, but it is not known whether raised plasma homocysteine 
      (HCY) found in patients with IBD significantly contributes to this activation. 
      The aim of this study was to investigate if HHCY or presence of the TT variant 
      significantly induces a hypercoagulable state in IBD patients receiving 
      anti-inflammatory therapy during active disease, and to study if genetic 
      determinants for thromboembolic disease are more frequent in these patients. 
      METHODS: The study was designed as a cross-sectional study in an outpatient 
      clinic comprising 106 IBD patients receiving anti-inflammatory therapy. Markers 
      of coagulation were measured in order to elucidate whether patients with HHCY or 
      the MTHFR TT variant were hypercoagulant compared with patients with no 
      impairment of HCY metabolism. In addition, markers of inflammation and 
      acute-phase reactants were measured in order to compare activity during active 
      disease and during remission. Genetic determinants of thromboembolic disease in 
      patients with IBD and in relevant controls were investigated in the expectation 
      of a more frequent occurrence of these markers of thrombophilia if 
      hypercoagulability could be a primary or contributory factor in IBD. RESULTS: No 
      significant difference could be found in coagulation activity, acute-phase 
      reactants or inflammatory markers in IBD patients with the TT variant of the 
      677C-->4T polymorphism or high (>15 micromol/L) plasma HCY levels, compared with 
      IBD patients with no impairment of HCY metabolism. In patients with IBD, the 
      coagulation activity was significantly increased during active disease compared 
      with a state of remission. As expected, a significant difference regarding 
      interleukin 6, C-reactive protein and erythrocyte sedimentation rate was present 
      in IBD, comparing active disease with a state of remission. No significant 
      complement activation was present in either of the groups or during active 
      disease. Neither of the allele frequencies of genetic determinants for 
      thrombophilia (coagulation factor V 1691G-->A (factor V Leiden) and factor II 
      20210G-->A polymorphisms) in the background population differed significantly 
      from that in IBD patients. CONCLUSIONS: This study found no correlation between 
      the MTHFR TT variant or HHCY and a hypercoagulable state in IBD patients 
      receiving anti-inflammatory treatment. This coagulation activity is high during 
      exacerbations of disease, but a considerable reduction is seen in patients on 
      anti-inflammatory therapy compared with non-treated patients. Coagulation 
      activation in IBD is probably a consequence of the inflammatory nature of the 
      disease. That thrombophilia could be a contributory or primary factor in the 
      development of IBD is not supported by the present study, as the frequencies for 
      the genetic determinants for thrombophilia are similar in IBD patients and 
      controls.
FAU - Bjerregaard, Larsen T
AU  - Bjerregaard LT
AD  - Dept of Clinical Biochemistry, Aalborg Hospital, Denmark. tblarsen@dadlnet.dk
FAU - Nederby, Nielsen J
AU  - Nederby NJ
FAU - Fredholm, L
AU  - Fredholm L
FAU - Brandslund, I
AU  - Brandslund I
FAU - Munkholm, P
AU  - Munkholm P
FAU - Hey, H
AU  - Hey H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Scand J Gastroenterol
JT  - Scandinavian journal of gastroenterology
JID - 0060105
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Blood Coagulation/*genetics/physiology
MH  - Cross-Sectional Studies
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Hyperhomocysteinemia/*complications/*genetics/physiopathology
MH  - Inflammatory Bowel Diseases/*complications/*genetics/physiopathology
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Genetic/genetics
MH  - Signal Transduction/*genetics/physiology
MH  - Thrombophilia/*complications/*genetics/physiopathology
EDAT- 2002/02/15 10:00
MHDA- 2002/07/27 10:01
CRDT- 2002/02/15 10:00
PHST- 2002/02/15 10:00 [pubmed]
PHST- 2002/07/27 10:01 [medline]
PHST- 2002/02/15 10:00 [entrez]
AID - 10.1080/003655202753387374 [doi]
PST - ppublish
SO  - Scand J Gastroenterol. 2002 Jan;37(1):62-7. doi: 10.1080/003655202753387374.