title: Quantitative trait analysis of polymorphisms in two bilirubin metabolism enzymes to physiologic bilirubin levels in Chinese newborns.
abstract: OBJECTIVE
  To explore the effects of variants in Uridine Diphosphate Glucuronosyl Transferase 1A1 (UGT1A1) and Heme Oxygenase-1 (HMOX1) on daily physiological bilirubin levels and bilirubin changes during the first week after birth in Chinese newborns. Both UGT1A1 and HMOX1 code rate-limiting enzymes in the bilirubin metabolism pathway.
  
  
  METHODS
  We conducted a retrospective quantitative trait study to analyze 4154 daily bilirubin values, 3129 bilirubin changes, and 11 polymorphisms of 988 newborns during the natural course of physiological hyperbilirubinemia.
  
  
  RESULTS
  For UGT1A1, we found minor allele A of rs4148323 (G211A, UGT1A1*6) contributed to higher daily bilirubin levels on days 4-6 (with contributions to variations increasing from 4.8% to 12.3%), minor allele T of rs887829 (c-364t) contributed to lower daily bilirubin levels for days 6 and 7 (with contributions to variations increasing from 7.0% to 10.2%) (P < .03 for all). In addition, minor alleles of rs887829 and (TA)n repeat (UGT1A1*28), and haplotype T-long-G at rs887829-(TA)n-rs4148323 were associated with a decrease in bilirubin levels from day 5 to day 6 (P < .01 for all). No contribution from HMOX1 was found.
  
  
  CONCLUSIONS
  Bilirubin levels and changes during the middle and late parts of the first week were attributed to variants and haplotypes in UGT1A1. This quantitative trait study may provide a more robust statistical method for determining the association of genetic factors and bilirubin kinetics to predict the development of neonatal bilirubin in early postnatal life.
authors.affiliation: Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Youyou
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Neonatology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, China.
authors.forename: San-Nan
authors.initials: SN
authors.lastname: Wang
authors.affiliation: Center for Reproduction and Genetics and Suzhou Maternal-Child Medical Center, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neonatology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, China; Department of Neonatology, Nanjing Medical University Affiliated BenQ Hospital, Suzhou, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Zha
authors.affiliation: Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Peng
authors.affiliation: Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Shilin
authors.initials: S
authors.lastname: Li
authors.affiliation: Center for Reproduction and Genetics and Suzhou Maternal-Child Medical Center, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China. Electronic address: lijin@fudan.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
mesh_terms: D044466:Asian People; D001663:Bilirubin / Q000378:metabolism*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006239:Haplotypes; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000235:genetics*; D008297:Male; D012189:Retrospective Studies; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D014453:Glucuronosyltransferase; D051547:Heme Oxygenase-1; D000099148:UGT1A1 Enzyme; C496541:HMOX1 protein, human