Association of HMOX1 gene promoter polymorphisms with hyperbilirubinemia in the early neonatal period

Yoshinori Katayama, Tomoyuki Yokota, Hui Zhao, Ronald J. Wong, David K. Stevenson, Mariko Ikeda, Hajime Nakamura, Kazumoto Iijima, Ichiro Morioka

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background Heme oxygenase (HO) is the rate-limiting enzyme in the heme degradation pathway that produces bilirubin. The promoter region of human heme oxygenase-1 (HMOX1) contains a polymorphic (GT)n repeat that can regulate gene expression. Here, we investigated the association of (GT)n repeat length in the HMOX1 promoter region with neonatal hyperbilirubinemia in a population of Japanese term neonates. Methods Using polymerase chain reaction and fragment analysis, we determined the number of (GT)n repeats in 149 Japanese neonates. To omit the effects of the G71R mutation in uridine diphosphoglucuronosyltransferase on hyperbilirubinemia, we excluded 41 neonates with the G71R mutation. As a result, 25 neonates with hyperbilirubinemia and 83 non-hyperbilirubinemic controls were included in this prospective case-control study. Allele and genotype frequencies of (GT)n repeats in the HMOX1 gene were compared between hyperbilirubinemic and non-hyperbilirubinemic control neonates. Results The prevalence of short alleles (<22 (GT)n repeats) was significantly higher in hyperbilirubinemic than in control neonates (18% vs 7%, P = 0.015). Hyperbilirubinemia was more frequent in homozygous or heterozygous short allele carriers than control neonates (28% vs 11%, respectively, P = 0.03). Possession of short alleles was significantly associated with the development of neonatal hyperbilirubinemia (OR, 3.1; 95%CI: 1.03-9.53). Conclusions Infants carrying short alleles (<22 (GT)n repeats) in the HMOX1 gene promoter region appear to be at a higher risk for developing neonatal hyperbilirubinemia.

Original languageEnglish
Pages (from-to)645-649
Number of pages5
JournalPediatrics International
Volume57
Issue number4
DOIs
Publication statusPublished - 01-01-2015

Fingerprint

Heme Oxygenase-1
Hyperbilirubinemia
Newborn Infant
Neonatal Hyperbilirubinemia
Genes
Alleles
Genetic Promoter Regions
Heme Oxygenase (Decyclizing)
Mutation
Uridine
Heme
Bilirubin
Gene Frequency
Case-Control Studies
Genotype
Gene Expression
Polymerase Chain Reaction
Enzymes
Population

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health

Cite this

Katayama, Yoshinori ; Yokota, Tomoyuki ; Zhao, Hui ; Wong, Ronald J. ; Stevenson, David K. ; Ikeda, Mariko ; Nakamura, Hajime ; Iijima, Kazumoto ; Morioka, Ichiro. / Association of HMOX1 gene promoter polymorphisms with hyperbilirubinemia in the early neonatal period. In: Pediatrics International. 2015 ; Vol. 57, No. 4. pp. 645-649.
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title = "Association of HMOX1 gene promoter polymorphisms with hyperbilirubinemia in the early neonatal period",
abstract = "Background Heme oxygenase (HO) is the rate-limiting enzyme in the heme degradation pathway that produces bilirubin. The promoter region of human heme oxygenase-1 (HMOX1) contains a polymorphic (GT)n repeat that can regulate gene expression. Here, we investigated the association of (GT)n repeat length in the HMOX1 promoter region with neonatal hyperbilirubinemia in a population of Japanese term neonates. Methods Using polymerase chain reaction and fragment analysis, we determined the number of (GT)n repeats in 149 Japanese neonates. To omit the effects of the G71R mutation in uridine diphosphoglucuronosyltransferase on hyperbilirubinemia, we excluded 41 neonates with the G71R mutation. As a result, 25 neonates with hyperbilirubinemia and 83 non-hyperbilirubinemic controls were included in this prospective case-control study. Allele and genotype frequencies of (GT)n repeats in the HMOX1 gene were compared between hyperbilirubinemic and non-hyperbilirubinemic control neonates. Results The prevalence of short alleles (<22 (GT)n repeats) was significantly higher in hyperbilirubinemic than in control neonates (18{\%} vs 7{\%}, P = 0.015). Hyperbilirubinemia was more frequent in homozygous or heterozygous short allele carriers than control neonates (28{\%} vs 11{\%}, respectively, P = 0.03). Possession of short alleles was significantly associated with the development of neonatal hyperbilirubinemia (OR, 3.1; 95{\%}CI: 1.03-9.53). Conclusions Infants carrying short alleles (<22 (GT)n repeats) in the HMOX1 gene promoter region appear to be at a higher risk for developing neonatal hyperbilirubinemia.",
author = "Yoshinori Katayama and Tomoyuki Yokota and Hui Zhao and Wong, {Ronald J.} and Stevenson, {David K.} and Mariko Ikeda and Hajime Nakamura and Kazumoto Iijima and Ichiro Morioka",
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Katayama, Y, Yokota, T, Zhao, H, Wong, RJ, Stevenson, DK, Ikeda, M, Nakamura, H, Iijima, K & Morioka, I 2015, 'Association of HMOX1 gene promoter polymorphisms with hyperbilirubinemia in the early neonatal period', Pediatrics International, vol. 57, no. 4, pp. 645-649. https://doi.org/10.1111/ped.12591

Association of HMOX1 gene promoter polymorphisms with hyperbilirubinemia in the early neonatal period. / Katayama, Yoshinori; Yokota, Tomoyuki; Zhao, Hui; Wong, Ronald J.; Stevenson, David K.; Ikeda, Mariko; Nakamura, Hajime; Iijima, Kazumoto; Morioka, Ichiro.

In: Pediatrics International, Vol. 57, No. 4, 01.01.2015, p. 645-649.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association of HMOX1 gene promoter polymorphisms with hyperbilirubinemia in the early neonatal period

AU - Katayama, Yoshinori

AU - Yokota, Tomoyuki

AU - Zhao, Hui

AU - Wong, Ronald J.

AU - Stevenson, David K.

AU - Ikeda, Mariko

AU - Nakamura, Hajime

AU - Iijima, Kazumoto

AU - Morioka, Ichiro

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Background Heme oxygenase (HO) is the rate-limiting enzyme in the heme degradation pathway that produces bilirubin. The promoter region of human heme oxygenase-1 (HMOX1) contains a polymorphic (GT)n repeat that can regulate gene expression. Here, we investigated the association of (GT)n repeat length in the HMOX1 promoter region with neonatal hyperbilirubinemia in a population of Japanese term neonates. Methods Using polymerase chain reaction and fragment analysis, we determined the number of (GT)n repeats in 149 Japanese neonates. To omit the effects of the G71R mutation in uridine diphosphoglucuronosyltransferase on hyperbilirubinemia, we excluded 41 neonates with the G71R mutation. As a result, 25 neonates with hyperbilirubinemia and 83 non-hyperbilirubinemic controls were included in this prospective case-control study. Allele and genotype frequencies of (GT)n repeats in the HMOX1 gene were compared between hyperbilirubinemic and non-hyperbilirubinemic control neonates. Results The prevalence of short alleles (<22 (GT)n repeats) was significantly higher in hyperbilirubinemic than in control neonates (18% vs 7%, P = 0.015). Hyperbilirubinemia was more frequent in homozygous or heterozygous short allele carriers than control neonates (28% vs 11%, respectively, P = 0.03). Possession of short alleles was significantly associated with the development of neonatal hyperbilirubinemia (OR, 3.1; 95%CI: 1.03-9.53). Conclusions Infants carrying short alleles (<22 (GT)n repeats) in the HMOX1 gene promoter region appear to be at a higher risk for developing neonatal hyperbilirubinemia.

AB - Background Heme oxygenase (HO) is the rate-limiting enzyme in the heme degradation pathway that produces bilirubin. The promoter region of human heme oxygenase-1 (HMOX1) contains a polymorphic (GT)n repeat that can regulate gene expression. Here, we investigated the association of (GT)n repeat length in the HMOX1 promoter region with neonatal hyperbilirubinemia in a population of Japanese term neonates. Methods Using polymerase chain reaction and fragment analysis, we determined the number of (GT)n repeats in 149 Japanese neonates. To omit the effects of the G71R mutation in uridine diphosphoglucuronosyltransferase on hyperbilirubinemia, we excluded 41 neonates with the G71R mutation. As a result, 25 neonates with hyperbilirubinemia and 83 non-hyperbilirubinemic controls were included in this prospective case-control study. Allele and genotype frequencies of (GT)n repeats in the HMOX1 gene were compared between hyperbilirubinemic and non-hyperbilirubinemic control neonates. Results The prevalence of short alleles (<22 (GT)n repeats) was significantly higher in hyperbilirubinemic than in control neonates (18% vs 7%, P = 0.015). Hyperbilirubinemia was more frequent in homozygous or heterozygous short allele carriers than control neonates (28% vs 11%, respectively, P = 0.03). Possession of short alleles was significantly associated with the development of neonatal hyperbilirubinemia (OR, 3.1; 95%CI: 1.03-9.53). Conclusions Infants carrying short alleles (<22 (GT)n repeats) in the HMOX1 gene promoter region appear to be at a higher risk for developing neonatal hyperbilirubinemia.

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U2 - 10.1111/ped.12591

DO - 10.1111/ped.12591

M3 - Article

VL - 57

SP - 645

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JF - Pediatrics International

SN - 1328-8067

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