title: Comprehensive variant screening of the UGT gene family.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Findings from the present study would be valuable for further studies on pharmacogenetic studies of personalized medicine and drug response.
authors: Department of Life Science, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 121-742, Korea. hdshin@sogang.ac.kr.
authors: Jason Yongha
authors: JY
authors: Kim
authors: Hyun Sub
authors: HS
authors: Cheong
authors: Byung Lae
authors: BL
authors: Park
authors: Lyoung Hyo
authors: LH
authors: Kim
authors: Suhg
authors: S
authors: Namgoong
authors: Ji On
authors: JO
authors: Kim
authors: Hae Deun
authors: HD
authors: Kim
authors: Young Hoon
authors: YH
authors: Kim
authors: Myeon Woo
authors: MW
authors: Chung
authors: Soon Young
authors: SY
authors: Han
authors: Hyoung Doo
authors: HD
authors: Shin
mesh_terms: D044466:Asian People / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D014453:Glucuronosyltransferase / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People / Q000235:genetics; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme; C491474:UGT2B7 protein, human; C472000:UDP-glucuronosyltransferase 2B15, human
keywords: SNP; UGT1A1; UGT2B15; UGT2B7; personalized medicine; uridine diphosphate glucuronyltransferase