Hyperhomocysteinemia and prevalence of polymorphisms of homocysteine metabolism-related enzymes in patients with inflammatory bowel disease.
OBJECTIVE
Patients with inflammatory bowel disease (IBD) have an increased risk of thrombotic complications. Moreover, a hypercoagulable state has been hypothesized as a contributing factor in the pathogenesis of IBD. Recently, a growing amount of interest has focused on mild-to-moderate hyperhomocysteinemia as a risk factor for thromboembolic disease. We aimed to evaluate the prevalence of hyperhomocysteinemia in patients with IBD and to investigate the contribution of genetic defects in the enzymes involved in homocysteine (Hcy) metabolism and vitamin status in determining increased levels of plasma total Hcy (tHcy).


METHODS
The concentrations of tHcy, folate, and vitamin B12 as well as the prevalence of methylenetetrahydrofolate reductase (MTHFR) 677C to T mutation and the 68-bp insertion at exon 8 of cystathionine beta-synthase (CBS) were measured in patients with IBD and healthy controls.


RESULTS
In all, 17 out of 64 IBD patients (26.5%) and four out of 121 (3.3%) controls had hyperhomocysteinemia with a statistically significant difference (p < 0.0001). No significant difference was found between IBD patients and controls with regard to the prevalence of homozygotes for the C677T variant (TT) of MTHFR or the prevalence of heterozygotes for the CBS-gene mutation (IN). Among the IBD patients the only independent factor significantly associated with hyperhomocysteinemia was folate deficiency (p = 0.0002), regardless of the MTHFR or the CBS genotype.


CONCLUSIONS
IBD patients have a higher prevalence of hyperhomocysteinemia than do healthy controls. Folate deficiency is the only independent risk factor in developing hyperhomocysteinemia.
Papa
A
A
Department of Internal Medicine, Catholic University of Rome, Italy.
De Stefano
V
V
Danese
S
S
Chiusolo
P
P
Persichilli
S
S
Casorelli
I
I
Zappacosta
B
B
Giardina
B
B
Gasbarrini
A
A
Leone
G
G
Gasbarrini
G
G
D000328:Adult; D000368:Aged; D005260:Female; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000453:epidemiology* / Q000235:genetics*; D015212:Inflammatory Bowel Diseases / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015995:Prevalence
D006710:Homocysteine