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KMID : 1132720070050040161
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Genomics & Informatics
2007 Volume.5 No. 4 p.161 ~ p.167
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Genetic Polymorphisms of UGT1A and their Association with Clinical Factors in Healthy Koreans
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Kim Jeong-Oh
Shin Jeong-Young
Lee Myung-Ah
Chae Hyun-Suk
Lee Chul-Ho
Roh Jae-Sook
Jin Sun-Kyung
Kang Tae-Sun
Choi Jung-Ran
Kang Jin-Hyoung
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Abstract
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Glucuronidation by the uridine diphosphateglucuronosyltransferase 1A enzymes (UGT1As) is a major pathway for
elimination of particular drugs and endogenous substances, such as bilirubin. We examined the relation of eight single
nucleotide polymorphisms (SNPs) and haplotypes of the UGT1A gene with their clinical factors. For association
analysis, we genotyped the variants by direct sequencing analysis and polymerase chain reaction (PCR) in 218 healthy Koreans. The frequency of UGT1A1 polymorphisms, -3279T>G, -3156G>A, -53 (TA)6>7, 211G>A, and 686C> A, was 0.26, 0.12, 0.08, 0.15, and 0.01, respectively. The frequency of -118 (T)9>10 of UGT1A9 was 0.62, which was significantly higher than that in Caucasians (0.39). Neither the -2152C>T nor the -275T>A polymorphism was observed in Koreans or other Asians in comparison with Caucasians. The -3156G>A and -53 (TA)6>7 polymorphisms of UGT1A were significantly associated with platelet count and total bilirubin level (p=0.01, p=0.01, respectively). Additionally, total bilirubin level was positively correlated with occurrence of the UGT1A9-118 (T)9>10 rare variant. Common haplotypes encompassing six UGT1A polymorphisms were significantly associated with total bilirubin level (p=0.01). Taken together, we suggest that
determination of the UGT1A1 and UGT1A9 genotypes is clinically useful for predicting the efficacy and serious toxicities of particular drugs requiring glucuronidation.
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KEYWORD
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Uridine diphosphate glucuronosyltransferases (UGT), single nucleotide polymorphism (SNP), haplotype, total bilirubin, glucuronidation
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