RT Journal Article SR Electronic T1 Sequence Variability and Candidate Gene Analysis in Two Cancer Patients with Complex Clinical Outcomes During Morphine Therapy JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 677 OP 680 DO 10.1124/dmd.31.5.677 VO 31 IS 5 A1 Takeshi Hirota A1 Ichiro Ieiri A1 Hiroshi Takane A1 Hiroyuki Sano A1 Katsuyuki Kawamoto A1 Hironao Aono A1 Akira Yamasaki A1 Hiromi Takeuchi A1 Mikio Masada A1 Eiji Shimizu A1 Shun Higuchi A1 Kenji Otsubo YR 2003 UL http://dmd.aspetjournals.org/content/31/5/677.abstract AB In this case report, we present genetic differences in two morphine-related gene sequences, UDP-glucuronosyltransferase 2B7 (UGT2B7) and μ opioid receptors (MOR1), in two cancer patients whose clinical responses to morphine were very different [i.e., sensitive (patient 1) and low responder (patient 2)]. In addition, allelic variants in the UGT2B7 gene were analyzed in 46 Japanese individuals. Amplified DNA fragments for the two genes of interest were screened using single strand conformation polymorphism and then sequenced. In theUGT2B7 gene, 12 single nucleotide polymorphisms (SNPs) were newly identified with an allelic frequency ranging from 0.022 to 0.978. Six SNPs in the promoter region (A-1302G, T-1295C, T-1111C, G-899A, A-327G, and T-125C) and two coding SNPs (UGT2B7*2 in exon 2 and C1059G in exon 4) appeared to be consistently linked. Remarkable differences in the nucleotide sequence of UGT2B7 were observed between the two patients; in contrast to patient 1 who had “reference” alleles at almost SNP positions, but a rare ATTGAT*2(AT)C haplotype as homozygosity, patient 2 was a homozygous carrier for the predominant GCCAGC*1(TC)G sequence. Serum morphine and two glucuronide concentrations in patient 2 suggest that the predominant GCCAGC*1G sequence was not associated with a “poor metabolizer” phenotype. In the MOR1 gene, patient 1 had no SNPs, whereas patient 2 was a heterozygous carrier for both the G-1784A and A118G alleles. The present study describes substantial differences in genotype patterns of two genes of interest between the two patients. The results necessitate larger trials to confirm these observations in larger case control studies. The American Society for Pharmacology and Experimental Therapeutics