Genomics Inform.  2007 Dec;5(4):161-167.

Genetic Polymorphisms of UGT1A and their Association with Clinical Factors in Healthy Koreans

• Kim JO
• Shin JY
• Lee MA
• Chae HS
• Lee CH
• Roh JS
• Jin SK
• Kang TS
• Choi JR
• Kang JH

Abstract

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.

Keyword

Uridine diphosphate glucuronosyltransferases (UGT); single nucleotide polymorphism (SNP); haplotype; total bilirubin; glucuronidation

MeSH Terms

Asian Continental Ancestry Group
Bilirubin
Genotype
Haplotypes
Humans
Platelet Count
Polymerase Chain Reaction
Polymorphism, Genetic*
Polymorphism, Single Nucleotide
Uridine
Bilirubin
Uridine