title: Homozygous variant of UGT1A1 gene mutation and severe neonatal hyperbilirubinemia.
abstract: BACKGROUND
  The aim of the present study was to compare, in a case-control study, the prevalence of nucleotide 211 guanine to adenine (G-->A) mutation of uridine diphosphoglucuronosyl transferase (UGT1A1) gene in Malaysian Chinese newborns with and without severe hyperbilirubinemia (total serum bilirubin >250 micromol/L during first 48 h of life or > or =300 micromol/L thereafter), and to determine whether this mutation was a significant risk factor associated with severe hyperbilirubinemia.
  
  
  METHODS
  Seventy-four term infants of Chinese descent admitted with severe hyperbilirubinemia were recruited. Infants without severe hyperbilirubinemia (n = 125) were randomly selected from among healthy Chinese term infants. UGT1A1 nucleotide 211 polymorphism was assayed using the Taqman single nucleotide polymorphism genotyping method. Using gestational age, types of feeds, G6PD mutation, G6PD enzyme levels, and UGT1A1 gene mutation status as independent variables, logistic regression analysis was carried out to determine the significant risk factors associated with severe hyperbilirubinemia.
  
  
  RESULTS
  UGT1A1 gene mutation was significantly more common among hyperbilirubinemic infants (39.2%) than controls (25.6%; P = 0.04). Gestational age (adjusted odds ratio [OR], 0.7; 95% confidence intervals [CI]: 0.5-0.9; P = 0.01), G6PD mutation (adjusted OR, 7.2; 95%CI: 2.7-19.0; P < 0.0001), exclusive breast-feeding (adjusted OR, 11.7; 95%CI: 2.7-49.9; P = 0.001), and homozygous variant of UGT1A1 gene mutation (adjusted OR, 32.2; 95%CI: 3.8-273.2; P = 0.001) were significant risk factors. Heterozygous variant of UGT1A1 gene mutation, actual levels of G6PD enzyme, and mixed feeding were not.
  
  
  CONCLUSIONS
  Homozygous variant of nucleotide 211 G-->A mutation of UGT1A1 gene is a significant risk factor associated with severe hyperbilirubinemia among Malaysian Chinese newborns.
authors.affiliation: Department of Paediatrics, Universiti Kebangsaan Malaysia, Jalan Yaacbo Latif, Kuala Lumpur, Malaysia. nemyun_boo@imu.edu.my
authors.forename: Nem-Yun
authors.initials: NY
authors.lastname: Boo
authors.forename: Fei-Liang
authors.initials: FL
authors.lastname: Wong
authors.forename: May-Kay
authors.initials: MK
authors.lastname: Wang
authors.forename: Ainoon
authors.initials: A
authors.lastname: Othman
mesh_terms: D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China / Q000208:ethnology; D014453:Glucuronosyltransferase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000235:genetics*; D007231:Infant, Newborn; D016015:Logistic Models; D008296:Malaysia / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme