Differences in UGT1A1, UGT1A7, and UGT1A9 polymorphisms between Uzbek and Japanese populations.

BACKGROUND AND OBJECTIVES

Uridine-diphosphate glucuronosyltransferase 1A (UGT1A) is a key enzyme involved in irinotecan metabolism, and polymorphisms in the UGT1A gene are associated with irinotecan-induced toxicity. The aim of this study was to elucidate the allele frequencies of UGT1A polymorphisms in healthy Uzbek volunteers, and to compare them with those of the Japanese population.

METHOD

A total of 97 healthy volunteers from Uzbekistan were enrolled and blood samples were collected from each participant. Genotyping analysis was performed by fragment size analysis for UGT1A128, direct sequencing for UGT1A73 and UGT1A922, and TaqMan assays for UGT1A193, UGT1A16, UGT1A127, UGT1A160, and UGT1A712. The frequencies of polymorphisms were compared with the Japanese population by using the data previously reported from our study group.

RESULTS

When the Uzbek and Japanese populations were compared, heterozygotes or homozygotes for UGT1A128, UGT1A160, and UGT1A193 were significantly more frequent in the Uzbek population (P < 0.01). The rate of UGT1A712 was not significantly different between the two populations, whereas UGT1A16 and UGT1A922 were significantly less frequent in the Uzbek population (P < 0.05). UGT1A7*1 were less prevalent in the Uzbek population than in the Japanese population (P < 0.01).

CONCLUSION

The Uzbek population has different frequencies of polymorphisms in UGT1A genes compared with the Japanese population. A comprehensive study of the influence of UGT1A1 polymorphisms on the risk of irinotecan-induced toxicity is necessary for optimal use of irinotecan treatment.