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


METHODS
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 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.


RESULTS
When 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).


CONCLUSIONS
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.
Department of Human Health and Medical Sciences, Kochi Medical School, Kohasu, Oko-cho, Nankoku, 783-8505, Japan.
Hiromichi
H
Maeda
Shoichi
S
Hazama
Abdiev
A
Shavkat
Ken
K
Okamoto
Koji
K
Oba
Junichi
J
Sakamoto
Kenichi
K
Takahashi
Masaki
M
Oka
Daisuke
D
Nakamura
Ryouichi
R
Tsunedomi
Naoko
N
Okayama
Hideyuki
H
Mishima
Michiya
M
Kobayashi
D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D005787:Gene Frequency; D014644:Genetic Variation; D005828:Genetics, Population; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D007564:Japan; D020641:Polymorphism, Single Nucleotide; D000090264:UDP-Glucuronosyltransferase 1A9; D014610:Uzbekistan; D044465:White People / Q000208:ethnology / Q000235:genetics*; D000099148:UGT1A1 Enzyme
D014453:Glucuronosyltransferase; D000090264:UDP-Glucuronosyltransferase 1A9; D000099148:UGT1A1 Enzyme; C000715591:UGT1A9 protein, human; C524630:UGT1A7 protein, human