Association of MTRR 66A>G polymorphism with superoxide dismutase and disease activity in patients with Crohn's disease.
OBJECTIVE
The aim of this study was to evaluate the association of nutritional (folate, vitamin B12) and genetic (MTHFR, MTR, MTRR, TCN) determinants of homocysteine metabolism and of superoxide dismutase with Crohn's disease (CD).


METHODS
One hundred forty patients with CD were compared with 248 matched healthy controls.


RESULTS
Plasma homocysteine levels were higher in CD patients than controls (11.8 vs 10.4 micromol/L, P= 0.0004). Vitamin B12 and folate levels were lower in CD subjects compared to controls (207 vs 255 pmol/L, P= 0.0082, and 8.6 vs 11 nmol/L, P= 0036, respectively). Patients with a personal history of ileal resection, ileitis, or colectomy had significantly lower vitamin B12 levels. In multivariate analysis, vitamin B12 and MTHFR 677 TT carriers were the two significant independent factors of plasma homocysteine >15 micromol/L in CD patients (P= 0.0187 and 0.0048, respectively). The significant association between homocysteine and vitamin B12 levels remained significant only in patients with the highest superoxide dismutase values (P < 0.0001). The MTRR AA genotype was a significant independent predictor of CD risk (odds ratio 3.7, 95% CI 1.218-11.649, P= 0.0213). The level of superoxide dismutase was significantly higher (P= 0.0143) and was correlated with Crohn's Disease Activity Index (CDAI) scores (P for trend = 0.0276) in patients carrying MTRR AA genotype.


CONCLUSIONS
Vitamin B12 and MTHFR 677 TT genotype are the main determinants of hyperhomocysteinemia in CD patients. The association of MTRR 66A>G polymorphism with oxidant stress and disease activity provides rationale for screening vitamin deficiencies in these patients.
Peyrin-Biroulet
Laurent
L
Inserm, U724, Laboratory of Cellular and Molecular Pathology in Nutrition, Faculty of Medicine, Vandoeuvre-les-Nancy, France.
Guéant-Rodriguez
Rosa-Maria
RM
Chen
Min
M
Bronowicki
Jean-Pierre
JP
Bigard
Marc-André
MA
Guéant
Jean-Louis
JL
D000328:Adult; D003424:Crohn Disease / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013482:Superoxide Dismutase / Q000378:metabolism*
D006710:Homocysteine; D013482:Superoxide Dismutase; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase