title: The association between heterozygosity for UGT1A1*6, UGT1A1*28, and variation in the serum total-bilirubin level in healthy young Japanese adults.
abstract: OBJECTIVE
  Considerable variations in the serum total-bilirubin concentrations are observed in healthy subjects. Both sex and the UGT1A1 homozygous genotypes,*6/*6 and *28/*28, are known to influence this variation. However, currently, there is no consensus on the relationship of the heterozygous genotypes *1/*6, *1/*28, or *6/*28 and interindividual variation in the serum total-bilirubin levels. In the present study, we sought to clarify the involvement of heterozygous alleles *6 and *28 in the interindividual difference in the serum total-bilirubin levels among healthy young Japanese adults.
  
  
  METHODS
  We enrolled 92 healthy Japanese aged 20-30 years (37 men and 55 women). The serum total-bilirubin levels were compared between men and women and with different UGT1A1 genotypes. Multiple regression analysis was used to investigate the relationships between individual differences in the serum total-bilirubin levels, UGT1A1 genetic variants, and sex.
  
  
  RESULTS
  Serum total-bilirubin levels were significantly lower in women than in men. There were also significant differences in the serum total-bilirubin levels between the *1/*1 and *1/*28 genotype, the *1/*1 and *6/*28 genotype, the *1/*6 and *1/*28 genotype, and also the *1/*6 and *6/*28 genotype. Multiple regression analysis showed significant relationships between the serum total-bilirubin level, the UGT1A1 genotypes *1/*28 and *6/*28, and sex. This model explained 42.3% of the interindividual variation in serum total-bilirubin levels.
  
  
  CONCLUSIONS
  We found that the UGT1A1 genotypes *1/*28 and *6/*28 as well as sex contributed to interindividual variations in the serum total-bilirubin levels. In contrast, UGT1A1*1/*6 showed only minimal involvement in individual differences in serum total-bilirubin levels.
authors.affiliation: Department of Pharmacy, Hokkaido Pharmaceutical University School of Pharmacy, Otaru, Japan. moriya@hokuyakudai.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Moriya
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Saito
authors.forename: Nuala
authors.initials: N
authors.lastname: Helsby
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Sugino
authors.forename: Michiaki
authors.initials: M
authors.lastname: Yamakage
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takasaki
authors.forename: Hidenori
authors.initials: H
authors.lastname: Kato
authors.forename: Nahoko
authors.initials: N
authors.lastname: Kurosawa
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People; D001663:Bilirubin / Q000097:blood*; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme