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

Most Taiwanese patients with hyper-bilirubinemia have genetic abnormalities in the uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene beyond the variants in the TATA box upstream of UGT1A1 associated with Gilbert’s syndrome. To investigate the role of UGT1A1 in the pathogenesis of indirect hyper-bilirubinemia, we prospectively studied 97 consecutive patients with indirect hyper-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 have Gilbert’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 coding region. Patients with higher serum total bilirubin are associated with higher likelihood of carrying Gilbert’s syndrome genotype: 60.0% (P=0.007) patients with serum total bilirubin level ≥2.5 mg/dL carried the Gilbert’s syndrome genotype, while only 23.9% of patients with serum total bilirubin level <2.5 mg/dL carry the same genotype (P=0.0006). Forty-one of the 61 non-Gilbert’s patients had one homogenous variants or two or more heterozygous variants in UGT1A1. Further studies are necessary to confirm the role of one homo-zygous variant or two or more hetero-zygous variants in UGT1A1 gene as factors for indirect hyper-bilirubinemia.