Yoshihiro Maruo1, Yoriko Morioka2, Hiroshi Fujito3, Sayuri Nakahara2, Takahide Yanagi2, Katsuyuki Matsui2, Asami Mori4, Hiroshi Sato5, Robert H Tukey6, Yoshihiro Takeuchi2. 1. Department of Pediatrics, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga, Japan. Electronic address: maruo@belle.shiga-med.ac.jp. 2. Department of Pediatrics, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga, Japan. 3. Department of Pediatrics, Hanwasumiyoshin General Hospital, Osaka, Japan; Department of Pediatrics, Hino Memorial Hospital, Kozukeda, Hino, Japan. 4. Department of Pediatrics, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga, Japan; Department of Pediatrics, Hino Memorial Hospital, Kozukeda, Hino, Japan. 5. Department of Health and Nutrition, Faculty of Health and Human Life, Nagoya Bunri University, Inazawa, Japan. 6. Departments of Pharmacology, Chemistry, and Biochemistry, University of California San Diego, La Jolla, CA.
Abstract
OBJECTIVE: To evaluate the role of bilirubin UDP-glucuronosyltransferase family 1, polypeptide A1 (UGT1A1) gene variations on prolonged unconjugated hyperbilirubinemia associated with breast milk feeding (breast milk jaundice [BMJ]). STUDY DESIGN: UGT1A1 gene allelic variation was analyzed in 170 Japanese infants with BMJ with polymerase chain reaction-direct sequencing, and their genotypes compared with serum bilirubin concentrations. In 62 of 170 infants, serum bilirubin concentration was followed after 4 months of life. Genotypes were examined in 55 infants without BMJ. RESULTS: Of 170 infants with BMJ, 88 (51.8%) were homozygous UGT1A1*6. Serum bilirubin concentrations (21.8 ± 3.65 mg/dL) were significantly greater than in infants with other genotypes (P < .0001). The Gilbert UGT1A1*28 allele was not detected in infants with BMJ, except in an infant who was compound heterozygous with UGT1A1*6. At 4 months of age, serum bilirubin concentration improved to >1 mg/dL, except in 2 infants who were homozygous UGT1A1*7. Homozygous UGT1A1*6 was not detected in the control group. CONCLUSION: One-half of the infants with BMJ were homozygous UGT1A1*6 and exhibited a serum bilirubin concentration significantly greater than other genotypes. This finding indicates that UGT1A1*6 is a major cause of BMJ in infants in East Asia. Previous finding have demonstrated that 5β-pregnane-3α,20β-diol present in breast milk inhibits p.G71R-UGT1A1 bilirubin glucuronidation activity. Thus, prolonged unconjugated hyperbilirubinemia may develop in infants with UGT1A1*6 who are fed breast milk.
OBJECTIVE: To evaluate the role of bilirubinUDP-glucuronosyltransferase family 1, polypeptide A1 (UGT1A1) gene variations on prolonged unconjugated hyperbilirubinemia associated with breast milk feeding (breast milk jaundice [BMJ]). STUDY DESIGN:UGT1A1 gene allelic variation was analyzed in 170 Japanese infants with BMJ with polymerase chain reaction-direct sequencing, and their genotypes compared with serum bilirubin concentrations. In 62 of 170 infants, serum bilirubin concentration was followed after 4 months of life. Genotypes were examined in 55 infants without BMJ. RESULTS: Of 170 infants with BMJ, 88 (51.8%) were homozygous UGT1A1*6. Serum bilirubin concentrations (21.8 ± 3.65 mg/dL) were significantly greater than in infants with other genotypes (P < .0001). The Gilbert UGT1A1*28 allele was not detected in infants with BMJ, except in an infant who was compound heterozygous with UGT1A1*6. At 4 months of age, serum bilirubin concentration improved to >1 mg/dL, except in 2 infants who were homozygous UGT1A1*7. Homozygous UGT1A1*6 was not detected in the control group. CONCLUSION: One-half of the infants with BMJ were homozygous UGT1A1*6 and exhibited a serum bilirubin concentration significantly greater than other genotypes. This finding indicates that UGT1A1*6 is a major cause of BMJ in infants in East Asia. Previous finding have demonstrated that 5β-pregnane-3α,20β-diol present in breast milk inhibits p.G71R-UGT1A1bilirubin glucuronidation activity. Thus, prolonged unconjugated hyperbilirubinemia may develop in infants with UGT1A1*6 who are fed breast milk.
Authors: Celia N Sanchez-Dominguez; Hugo L Gallardo-Blanco; Mauricio A Salinas-Santander; Rocio Ortiz-Lopez Journal: Exp Ther Med Date: 2018-05-18 Impact factor: 2.447
Authors: Adrian Castillo; Tristan R Grogan; Grace H Wegrzyn; Karrie V Ly; Valencia P Walker; Kara L Calkins Journal: PLoS One Date: 2018-06-01 Impact factor: 3.240