Differences in UGT1A1, UGT1A7, and UGT1A9 Polymorphisms between Uzbek and Japanese Populations

Abstract

Background and ObjectivesUridine-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.MethodA 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 UGT1A1*28, direct sequencing for UGT1A7*3 and UGT1A9*22, and TaqMan assays for UGT1A1*93, UGT1A1*6, UGT1A1*27, UGT1A1*60, and UGT1A7*12. The frequencies of polymorphisms were compared with the Japanese population by using the data previously reported from our study group.ResultsWhen the Uzbek and Japanese populations were compared, heterozygotes or homozygotes for UGT1A1*28, UGT1A1*60, and UGT1A1*93 were significantly more frequent in the Uzbek population (P < 0.01). The rate of UGT1A7*12 was not significantly different between the two populations, whereas UGT1A1*6 and UGT1A9*22 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).ConclusionThe 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.

Effects of UGT1A1, CYP3A5 and ABCB1 Genetic Variants on Pharmacokinetics of Antihistamine Drug Mizolastine in Chinese Healthy Volunteers

“…Moreover, these results show that the frequency of UGT1A1*6 variant allele (14.6%, i.e. 7/(24 9 2) %) was similar to that reported in Chinese and Japanese while significantly different from Caucasians (0.07%, p < 0.05) and Africans in UGT1A1*6 allele variants (0.00%, p < 0.05) [16,42,43]. These results support the previous opinion that the allele UGT1A1*6 was more frequent in Asian ethnic groups, while it was missing or there were very few in Caucasians or Africans, suggesting that this genetic mutation might be involved in the interindividual differences of substrate drug such as mizolastine pharmacokinetics in Chinese volunteers.…”

Ataluren Pharmacokinetics in Healthy Japanese and Caucasian Subjects

“…One UGT1A9 polymorphism (UGT1A9*22) has been reported to be present only in Japanese populations; however, the allele frequency of this polymorphism is less than 0.7% in the Japanese population 33,34 ; therefore, polymorphisms of UGT1A9 are not expected to influence the PK of ataluren in Japanese subjects. Ataluren is metabolized via UGT enzymes, mainly by UGT1A9.…”

Rapid and sensitive detection of UGT1A1 polymorphisms associated with irinotecan toxicity by a novel DNA microarray

“…We developed an additional DNA microarray capable of simultaneously detecting UGT1A polymorphisms at seven loci: UGT1A1*6 (211G > A, rs4148323), UGT1A1*27 (686C > A, rs35350960), UGT1A1*28 (TA 6 > TA7, rs8175347), UGT1A1*60 (−3279T > G, rs4124874), UGT1A7 (−57T > G, rs7586110), UGT1A7 (387T > G, rs17868323), and UGT1A9*1b (−118T 9 > T 10 , rs3832043, also called UGT1A9*22 ) . For this, seven sets of primers and probes were used (Table ).…”

“…and UGT1A9*1b (À118T 9 > T 10 , rs3832043, also called UGT1A9*22). (26,29,30) For this, seven sets of primers and probes were used ( Table 2). In the first PCR reaction, genomic DNA was amplified with Cy5-labeled dCTP (GE Healthcare Japan, Tokyo, Japan).…”

“…(24) The relative frequency of UGT1A variants varies between Caucasian and Asian populations, and UGT1A1*6 is reportedly strongly associated with severe neutropenia in Asian patients in particular. (10,25,26) In this study, using a DNA array technique, we accurately and simultaneously detected both the 2-bp repeated sequence insertion and single nucleotide polymorphism (SNP) in UGT1A.…”