Prevalence of polymorphisms in the human UDP-glucuronosyltransferase 2B family: UGT2B4((DE)-E-458), UGT2B7((HY)-Y-268), and UGT2B15((DY)-Y-85)

UDP-glucuronosyltransferases (UGTs) of the UGT2B family conjugate steroid h ormones as well as bile acids and xenobiotics, UGT2Bs are expressed in nume rous human tissues, such as skin, breast, prostate, adipose, and intestine and are hypothesized to modulate steroid metabolism and excretion. Polymorp hisms have been identified that may modify substrate specificities or enzym e activities of UGT2B family isozymes, We determined the prevalence of the UGT2B4((DE)-E-458), UGT2B7((HY)-Y-268), and UGT2B15((DY)-Y-85) polymorphism s in a sample of 233 individuals. The allele frequencies were significantly different (P < 0.02) between individuals of Caucasian and Asian descent fo r all three polymorphisms. In Asians (n = 32), the frequencies of the UGT2B 4(D-458), UGT2B7(H-268), and UGT2B15(D-85) alleles were 1.00, 0.73, and 0.6 4, respectively, whereas, in Caucasians (n = 202), the frequencies of UGT2B 4(D-458), UGT2B7(H-268), and UGT2B15(D-85) were 0.75, 0.46, and 0.45, respe ctively. The distribution of the UGT2B4((DE)-E-458), UGT2B7((HY)-Y-268), an d UGT2B15((DY)-Y-85) genotypes also differed by ethnic group (P < 0.0001, P = 0.002, and P = 0.02, respectively). All Asians were homozygous for UGT2B 4(D458) and had a greater than 2-fold higher prevalence of the UGT2B7(H-268 ) and UGT2B15(D-85) homozygous genotypes compared with Caucasians: 56.2% ve rsus 21.8%, and 46.9% versus 22.3%, respectively. Concomitantly, only 9.4% of Asians were UGT2B7(Y-268) homozygous and 18.7% were UGT2B15(Y-85) homozy gous compared with 29.2% and 32.2%, respectively, of Caucasians, The data s uggest that there may be large differences in UGT2B polymorphisms between A sians and Caucasians, This warrants evaluation both in larger, multiethnic cohorts and in relation to known ecological differences in risk of sex horm one-dependent cancers.