Association of neonatal hyperbilirubinemia in breast-fed infants with UGT1A1 or SLCOs polymorphisms.
Neonates have physiologically increased bilirubin production and immature bilirubin metabolism, and present hyperbilirubinemia in association with genetic and or epigenetic factors. We previously reported that maximal body weight loss (inadequate feeding) is an independent risk factor for the development of hyperbilirubinemia in breast-fed Japanese neonates, and the UGT1A1 211G>A genotype becomes a risk factor under conditions of inadequate feeding. We extended the study to the association of other genetic factors, the UGT1A1 (TA)7 and solute-carrier organic anion transporters (SLCOs) polymorphisms with neonatal hyperbilirubinemia. We enrolled 401 full-term Japanese infants who were exclusively breastfeeding and classified them into two groups based on the degree of maximal body weight loss. We analyzed the clinical characteristics and UGT1A1 and SLCOs genotypes. Statistical analysis revealed that maximal body weight loss is the only independent risk factor for the development of neonatal hyperbilirubinemia. UGT1A1, SLCO1B1 and SLCO1B3 polymorphisms become risk factors in neonates showing 10% or greater body weight loss during the neonatal period. Inadequate feeding may increase the bilirubin burden and cause apparent hyperbilirubinemia in neonates, who have a polymorphic change in the genes involved in the transport and/or metabolism of bilirubin.
Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.
Hiroko
H
Sato
Department of Pediatrics, Yamagata Prefectural Central Hospital, Yamagata, Japan.
Toshihiko
T
Uchida
Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.
Kentaro
K
Toyota
Statistical genetics and genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
Tomohiro
T
Nakamura
Statistical genetics and genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
Gen
G
Tamiya
Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.
Miyako
M
Kanno
Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.
Taeko
T
Hashimoto
Department of Pediatrics, Yamagata Prefectural Central Hospital, Yamagata, Japan.
Masashi
M
Watanabe
Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.
Kuraaki
K
Aoki
Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.
Kiyoshi
K
Hayasaka
D001663:Bilirubin / Q000235:genetics / Q000378:metabolism; D001942:Breast Feeding / Q000009:adverse effects*; D044127:Epigenesis, Genetic; D005260:Female; D056726:Genetic Association Studies; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000209:etiology / Q000235:genetics*; D007231:Infant, Newborn; D007564:Japan; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D027361:Organic Anion Transporters / Q000235:genetics*; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D015431:Weight Loss / Q000235:genetics; D000099148:UGT1A1 Enzyme
D001663:Bilirubin; D014453:Glucuronosyltransferase; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D000099148:UGT1A1 Enzyme; C503999:SLCO1B1 protein, human; C421209:SLCO1B3 protein, human