Multiple variants in UGT1A1 gene are factors to develop indirect hyper-bilirubinemia

Most Taiwanese patients with hyper-bilirubinemia have genetic abnormalities in the uridinediphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene beyond the variants in the TATAbox upstream of UGT1A1 associated with Gilbert’s syndrome. To investigate the role of UGT1A1 in thepathogenesis of indirect hyper-bilirubinemia, we prospectively studied 97 consecutive patients with indirecthyper-bilirubinemia for genotypes of promoter [(TA)6TAA6, (TA)7TAA7] and coding region [nucleotide(nt)-211, nt-686, nt-1,091 and nt-1,456] of UGT1A1. Thirty-six of the patients (45.6%) were found to haveGilbert’s syndrome with 7/7 genotype; among them, 14 also carried variants at nt-686. Forty-two patients(43.3%) had the 6/7 genotype; among them, 36 patients were found to have one or more variants in the codingregion. Patients with higher serum total bilirubin are associated with higher likelihood of carrying Gilbert’ssyndrome genotype: 60.0% (P=0.007) patients with serum total bilirubin level ≥2.5 mg/dL carried the Gilbert’ssyndrome genotype, while only 23.9% of patients with serum total bilirubin level 2.5 mg/dL carry the samegenotype (P=0.0006). Forty-one of the 61 non-Gilbert’s patients had one homogenous variants or two or moreheterozygous variants in UGT1A1. Further studies are necessary to confirm the role of one homo-zygousvariant or two or more hetero-zygous variants in UGT1A1 gene as factors for indirect hyper-bilirubinemia.