Yonsei Med J.  2014 Jan;55(1):232-239. 10.3349/ymj.2014.55.1.232.

Comprehensive Variant Screening of the UGT Gene Family

• Kim JY
• Cheong HS
• Park BL
• Kim LH
• Namgoong S
• Kim JO
• Kim HD
• Kim YH
• Chung MW
• Han SY
• Shin HD

• KMID: 1779911
• DOI: http://doi.org/10.3349/ymj.2014.55.1.232

Abstract

PURPOSE
UGT1A1, UGT2B7, and UGT2B15 are well-known pharmacogenes that belong to the uridine diphosphate glucuronyltransferase gene family. For personalized drug treatment, it is important to study differences in the frequency of core markers across various ethnic groups. Accordingly, we screened single nucleotide polymorphisms (SNPs) of these three genes and analyzed differences in their frequency among five ethnic groups, as well as attempted to predict the function of novel SNPs.
MATERIALS AND METHODS
We directly sequenced 288 subjects consisting of 96 Korean, 48 Japanese, 48 Han Chinese, 48 African American, and 48 European American subjects. Subsequently, we analyzed genetic variability, linkage disequilibrium (LD) structures and ethnic differences for each gene. We also conducted in silico analysis to predict the function of novel SNPs.
RESULTS
A total of 87 SNPs were detected, with seven pharmacogenetic core SNPs and 31 novel SNPs. We observed that the frequencies of UGT1A1 *6 (rs4148323), UGT1A1 *60 (rs4124874), UGT1A1 *93 (rs10929302), UGT2B7 *2 (rs7439366), a part of UGT2B7 *3 (rs12233719), and UGT2B15 *2 (rs1902023) were different between Asian and other ethnic groups. Additional in silico analysis results showed that two novel promoter SNPs of UGT1A1 -690G>A and -689A>C were found to potentially change transcription factor binding sites. Moreover, 673G>A (UGT2B7), 2552T>C, and 23269C>T (both SNPs from UGT2B15) changed amino acid properties, which could cause structural deformation.
CONCLUSION
Findings from the present study would be valuable for further studies on pharmacogenetic studies of personalized medicine and drug response.

Keyword

SNP; uridine diphosphate glucuronyltransferase; UGT1A1; UGT2B7; UGT2B15; personalized medicine

MeSH Terms

Asian Continental Ancestry Group/genetics
European Continental Ancestry Group/genetics
Female
Gene Frequency/genetics
Glucuronosyltransferase/*genetics
Haplotypes/genetics
Humans
Linkage Disequilibrium/genetics
Male
Polymorphism, Single Nucleotide/*genetics
Glucuronosyltransferase

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