{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T16:12:48Z","timestamp":1783440768521,"version":"3.54.6"},"reference-count":22,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2004,5,13]],"date-time":"2004-05-13T00:00:00Z","timestamp":1084406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2004,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background and Aim:\u2002<\/jats:bold> Numerous mutations of bilirubin uridine diphosphate\u2010glucuronosyltransferase gene (<jats:italic>UGT1A1<\/jats:italic>) have been reported in patients with familial unconjugated hyperbilirubinemia. The <jats:italic>UGT1A1<\/jats:italic> mutation appears to be considerably different among ethnic groups. To clarify the incidence of this gene mutation in the Japanese population, the presence of <jats:italic>UGT1A1<\/jats:italic> mutation was investigated in a group of Japanese patients with Crigler\u2013Najjar syndrome type 2 (CNS2) and Gilbert's syndrome (GS), as well as in healthy anicteric subjects.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Four patients with CNS2, 63 patients with GS, and 71 healthy subjects were enrolled in the study. The promoter and coding regions of <jats:italic>UGT1A1<\/jats:italic> were amplified by polymerase chain reaction (PCR) from genomic DNA isolated from leukocytes. The PCR products were directly sequenced by a dye terminating method. The UGT1A1 enzyme activity was determined in COS7 cells transfected with wild or P364L (1091 C\u2003&gt;\u2003T) mutant DNA.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> Homozygous Y486D was observed in all four patients with CNS2. The GS patients had <jats:italic>UGT1A1<\/jats:italic> mutations with 13 different genotypes in the promoter and coding region. Homozygous TA insertion in the TATA box (TA7) of the promoter region (TA7\/7; 33%), homozygous G71R (9%), and combination of TA7\/6 and heterozygous G71R (17%) were the most frequent findings in GS patients. Homozygous or heterozygous Y486D (8%) and P229Q (8%) were also observed in GS. A novel mutation, heterozygous P364L, was also identified in a GS patient. In addition to GS patients, homozygous or heterozygous TA7, G71R, and heterozygous Y486D were also observed in healthy subjects. The allele frequency of G71R and TA7 was 0.183 and 0.113 in healthy subjects, respectively. The P364L UGT1A1 enzyme activity was 64.4% lower than the wild\u2010type enzyme activity.<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> Polymorphisms in the coding region of <jats:italic>UGT1A1<\/jats:italic> were commonly observed in Japanese patients with GS and in healthy subjects. The genetic basis of hyperbilirubinemia appears to be different between the Japanese and Caucasian populations.<\/jats:p>","DOI":"10.1111\/j.1440-1746.2004.03370.x","type":"journal-article","created":{"date-parts":[[2004,8,10]],"date-time":"2004-08-10T09:38:46Z","timestamp":1092130726000},"page":"1023-1028","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["Genetic polymorphisms of bilirubin uridine diphosphate\u2010glucuronosyltransferase gene in Japanese patients with Crigler\u2013Najjar syndrome or Gilbert's syndrome as well as in healthy Japanese subjects"],"prefix":"10.1111","volume":"19","author":[{"given":"KEISUKE","family":"TAKEUCHI","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YOSHINAO","family":"KOBAYASHI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SHIGENORI","family":"TAMAKI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"TOMOAKI","family":"ISHIHARA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YOSHIHIRO","family":"MARUO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JUN","family":"ARAKI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RUMI","family":"MIFUJI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"TOSHIO","family":"ITANI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MAKOTO","family":"KURODA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HIROSHI","family":"SATO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MASAHIKO","family":"KAITO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YUKIHIKO","family":"ADACHI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,8,10]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115829"},{"key":"e_1_2_6_3_2","doi-asserted-by":"crossref","first-page":"23573","DOI":"10.1016\/S0021-9258(19)49501-X","article-title":"A phenylalanine codon deletion at the UGT1 gene complex locus of a Crigler\u2013Najjar type I patient generates a pH\u2010sensitive bilirubin UDP\u2010glucuronosyltransferase","volume":"268","author":"Ritter JK","year":"1993","journal-title":"J. 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