Debrisoquine oxidation polymorphism in patients with chronic inflammatory bowel disease.

Abstract

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 and chronic inflammatory bowel disease (CIBD), 67 (39 males) patients with ulcerative colitis (UC), 52 (35 males) patients with Crohn's disease (CD) and 837 healthy controls (391 males) received 10 mg debrisoquine. DBQ and its metabolite, 4-OH-DBQ, were measured in urine to calculate metabolic ratio. Subjects with MR < 12.6 (log 10 MR < 1.1) were extensive metabolizers (EM) of DBQ, whereas those with MR < 12.6 were poor metabolizers (PM). Four UC (5.97%), 1 CD (1.92%) patients and 42 controls (5.03%) were PM of DBQ (nonsignificant difference). When analysing the EM subjects separately, log10 MR were lower in controls (mean = -0.295, SD 0.427, P = 0.0015)) and in Crohn's disease patients (man = -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 phenotype of DBQ and the risk for CIBD. Nevertheless, the EM phenotype includes both homo- and heterozygote genotypes for functioning alleles exerting a gene-dose effect that gives a higher oxidative capability to homozygote EMs, reflected in a lower MR value. Genotyping studies are needed to disclose whether heterozygote EMs are over-represented among UC patients and to identify any nonfunctioning allele possibly linked to the risk of developing this disease.