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Association of HMOX1 gene promoter polymorphisms with hyperbilirubinemia in the early neonatal period
Author(s) -
Katayama Yoshinori,
Yokota Tomoyuki,
Zhao Hui,
Wong Ronald J,
Stevenson David K,
TaniguchiIkeda Mariko,
Nakamura Hajime,
Iijima Kazumoto,
Morioka Ichiro
Publication year - 2015
Publication title -
pediatrics international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.49
H-Index - 63
eISSN - 1442-200X
pISSN - 1328-8067
DOI - 10.1111/ped.12591
Subject(s) - hmox1 , heme oxygenase , medicine , genotype , allele , bilirubin , promoter , gene , mutation , pathogenesis , microbiology and biotechnology , heme , endocrinology , genetics , biology , gene expression , enzyme , biochemistry
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 J apanese 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.