title: Functional Study of Haplotypes in UGT1A1 Promoter to Find a Novel Genetic Variant Leading to Reduced Gene Expression.
abstract: BACKGROUND
  Uridine diphosphate glucuronyltransferase 1 family, A1 (UGT1A1) encodes for an enzyme that is a part of glucuronidation pathway, and a number of studies have shown that the promoter polymorphisms of UGT1A1 are associated with various diseases and drug response. In this study, we examined a possible association between UGT1A1 promoter haplotypes and the gene expression level.
  
  
  METHODS
  To identify promoter haplotype structure population, we directly sequenced the promoter region of UGT1A1 in 192 healthy Korean to identify 10 UGT1A1 promoter single-nucleotide polymorphisms (SNPs). Then, we genotyped the 10 SNPs in additional 192 non-Korean samples comprised of Chinese, Japanese, European American, and African American, and constructed haplotype structures. Furthermore, we conducted luciferase assay for the promoter SNP haplotypes to examine a possible expression change.
  
  
  RESULTS
  rs3755319C-rs2003569A-rs887829C-rs8175347(TA)6 (6.60 ± 0.15) and rs3755319A-rs2003569 G-rs887829C-rs8175347(TA)7 (2.79 ± 0.97) led to significantly lower gene expression when compared with rs3755319C-rs2003569 G-rs887829T-rs8175347(TA)6 (8.28 ± 0.60).
  
  
  CONCLUSIONS
  Our result suggests that the haplotypes in UGT1A1 promoter region can affect the expression level of the gene and drug metabolism associated with UGT1A1. Furthermore, in addition to rs8175347, rs3755319 was found to induce lower gene expression of UGT1A1.
authors.affiliation: *Division of Clinical Research, Department of Toxicological Evaluation and Research, Korea Ministry of Food and Drug Safety, Osong, Chungcheongbuk-do; †Department of Life Science, Sogang University; and ‡Department of Genetic Epidemiology, SNP Genetics, Inc, Seoul, Korea.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Shin
authors.forename: Jason Yongha
authors.initials: JY
authors.lastname: Kim
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.forename: Han Sung
authors.initials: HS
authors.lastname: Na
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Myeon Woo
authors.initials: MW
authors.lastname: Chung
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D044466:Asian People / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D044465:White People / Q000235:genetics; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme