DEBRISOQUINE OXIDATION POLYMORPHISM IN PATIENTS WITH CHRONIC INFLAMMATORY BOWEL-DISEASE

Polymorphic hydroxylation of debrisoquine (DBQ) is a Mendelian genetic trait related to the risk of suffering some spontaneous disorders. To elucidate whether such a relation exists between this polymorphism an d chronic inflammatory bowel disease (CIBD), 67 (39 males) patients wi th ulcerative colitis (UC), 52 (35 males) patients with Crohn's diseas e (CD) and 837 healthy controls (391 males) received 10 mg debrisoquin e. DBQ and its metabolite, 4-OH-DBQ, were measured in urine to calcula te metabolic ratio. Subjects with MR<12.6 (log 10 MR<1.1) were extensi ve metabolizers (EM) of DBQ, whereas those with MR>12.6 were poor meta bolizers (PM). Four Dc (5.97%), 1 CD (1.92%) patients and 42 controls (5.03%) were PM of DBQ (nonsignificant difference). When analysing the EM subjects separately, log 10 MR were lower in controls (mean = -0.2 95, SD 0.427, P = 0.0015)) and in Crohn's disease patients (mean = -0. 281, SD 0.495, P = 0.03) than in ulcerative colitis patients (mean = - 0.085, SD = 0.495). There is no relationship between oxidative phenoty pe of DBQ and the risk for CIBD. Nevertheless, the EM phenotype includ es both homo- and heterozygote genotypes for functioning alleles exert ing a gene-dose effect that gives a higher oxidative capability to hom ozygote EMs, reflected in a lower MR value. Genotyping studies are nee ded to disclose whether heterozygote EMs are overrepresented among UC patients and to identify any nonfunctioning allele possibly linked to the risk of developing this disease.