Neonatal hyperbilirubinemia in Japanese neonates: analysis of the heme oxygenase-1 gene and fetal hemoglobin composition in cord blood.
Neonatal hyperbilirubinemia is frequent and severe in Japanese infants. Although the G71R mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene is associated with severe neonatal hyperbilirubinemia in this population, it accounts for only half of the neonates with severe hyperbilirubinemia. It was suggested that increased bilirubin production would also be associated with severe neonatal hyperbilirubinemia in Japanese infants. To elucidate the genetic factors causing severe hyperbilirubinemia in these patients, we studied two notable factors associated with bilirubin production: heme oxygenase-1, a key enzyme of heme metabolism, and fetal Hb composition, a factor possibly associated with heme load in neonates. We first determined the sequences of promoter and all coding regions of the heme oxygenase-1 gene in Japanese neonates who had undergone phototherapy, but found no mutation except for the polymorphic (GT)n repeats in the promoter region. These repeats modulate the transcription of the heme oxygenase-1 gene, and the longer repeat sequences are known to reduce the transcription. We detected a significant difference in the allele frequencies of each number of (GT)n repeats between Japanese and German populations. However, we could not find a relation between those polymorphisms and neonatal hyperbilirubinemia. We next analyzed the state of Hb switching of the gamma- to beta-globin chain and the phenotype of gamma-globin chain isoforms in cord blood. We found no relation between fetal Hb composition and neonatal hyperbilirubinemia. Further studies are required to elucidate genetic or environmental factors in neonatal hyperbilirubinemia in Japanese infants.
Department of Pediatrics, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan. hayasaka@med.id.yamagata-u.ac.jp
Masayo
M
Kanai
Kazuhiro
K
Akaba
Ayako
A
Sasaki
Michihiko
M
Sato
Teruo
T
Harano
Shigeki
S
Shibahara
Hirohisa
H
Kurachi
Tadashi
T
Yoshida
Kiyoshi
K
Hayasaka
D002851:Chromatography, High Pressure Liquid; D005312:Fetal Blood / Q000378:metabolism*; D005319:Fetal Hemoglobin / Q000378:metabolism*; D005787:Gene Frequency; D005838:Genotype; D005858:Germany; D005914:Globins / Q000235:genetics; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D006801:Humans; D007231:Infant, Newborn; D007564:Japan; D007567:Jaundice, Neonatal / Q000378:metabolism* / Q000628:therapy; D008565:Membrane Proteins; D010789:Phototherapy; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012720:Severity of Illness Index
D008565:Membrane Proteins; D005914:Globins; D005319:Fetal Hemoglobin; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1