| Genetic Polymorphisms of UGT1A and their Association with Clinical Factors in Healthy Koreans. |
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Jeong Oh Kim, Jeong Young Shin, Myung Ah Lee, Hyun Suk Chae, Chul Ho Lee, Jae Sook Roh, Sun Kyung Jin, Tae Sun Kang, Jung Ran Choi, Jin Hyoung Kang |
1Laboratory of Medical Oncology, Catholic Research Institutes of Medical Science, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea. jinkang@catholic.ac.kr
2Medical Oncology, Kangnam St. Mary's Hospital, Korea.
3Gastroenterology, Uijeongbu St. Mary's Hospital, 65-1, Geumo-dong, Uijeongbu, Gyeonggi-do, Korea.
4Department of Clinical Genetics, School of Medicine, Yonsei University, 250 Seongsanno, Sudaemun-gu, Seoul 120-752, Korea.
5KFDA, NITR, Team of Clinical Pharmacology, 194 Tongil-no, Eunpyung-gu, Seoul 122-704, Korea. |
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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. |
| Keywords:
Uridine diphosphate glucuronosyltransferases (UGT); single nucleotide polymorphism (SNP); haplotype; total bilirubin; glucuronidation |
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