Linkage between A(TA)_7TAA and - 3279T > G mutations in UGT1A1 is not essential for pathogenesis of Gilbert syndrome

摘要

To the editor:Homozygous mutation A(TA)_7TAA (briefly (TA)_7) in the promoter of the UGT1A1 gene encoding the bilirubin UDP-glucuronosyl transfer-ase is considered to be the cause of the Gilbert syndrome (OMIM 143500) in the vast majority of affected Caucasians (1). An enhancer polymorphism ? 3279T/G responsible for additional lowering of the transcriptional activity of UGT1A1 was identified in a subset of patients with Gilbert syndrome (2). Maruo et al. (3) suggested that the linkage of - 3279G with (TA)7 is essential for the pathogenesis of Gilbert syndrome. The authors investigated 63 Caucasian and Japanese subjects. All 23 patients with Gilbert syndrome (11 Caucasians) were homozygous for (TA)_7 and - 3279G alleles. In contrast, none of the 40 control subjects (10 Caucasians) was homozygous for either of the mutations (Table 1). These findings may have important clinical implications because in case of perfect linkage, the genetic diagnosis of Gilbert syndrome could be easily established by PCR-RFLP genotyping of the - 3279T/G locus.