Korean J Pediatr.  2005 Apr;48(4):380-386.

The Association of Neonatal Hyperbilirubinemia with UGT1A1 and CYP1A2 Gene Polymorphism in Korean Neonates

• Kang H
• Lim JH
• Kim JS
• Kim ER
• Kim SD
• Lee HJ
• Chung JH

Abstract

PURPOSE
The incidence of nonphysiologic neonatal hyperbilirubinemia is twice as high in East Asians as in whites. Recently, UGT1A1 mutation was found to be a risk factor for neonatal hyperbilirubinemia. In congenitally-jaundiced Gunn rats, which lack expression of UDP-glucuronosyltransferase, alternative pathways can be stimulated by inducers of CYP1A1 and CYP1A2 enzymes. CYP1A2 plays a major role in bilirubin degradation of the alternate pathway. We studied the relationship between UGT1A1 and CYP1A2 gene polymorphism of neonatal hyperbilirubinemia in Koreans.
METHODS
Seventy-nine Korean full term neonates who had hyperbilirubinemia(serum bilirubin >12 mg/dL) without obvious causes of jaundice, were analyzed for UGT1A1 and CYP1A2 gene polymorphism; the control group was sixty-eight. We detected the polymorphism of Gly71Arg of UGT1A1 gene by direct sequencing and T2698G of CYP1A2 by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) using MboII and direct sequencing.
RESULTS
Allele frequency of Gly71Arg mutation in the hyperbilirubinemia group was 32 percent, which was significantly higher than 11 percent in the control group(P<0.0001). Mutant gene frequency of T2698G was 41.8 percent in patients and 32.3 percent in the control group(P=0.015), but allele frequency was 21 percent in patients and 19 percent in the control group, which was not significantly higher(P=0.706). There was no relationship between mutations of two genes(P=0.635).
CONCLUSION
The polymorphism of UGT1A1 gene(Gly71Arg) and CYP1A2 gene(T2698G) was detected in Korean neonatal hyperbilirubinemia. Only polymorphisms of Gly71Arg in UGT1A1 were significantly higher than control group.

Keyword

UGT1A1; CYP1A2; Neonatal hyperbilirubinemia; Polymorphism

MeSH Terms

Asian Continental Ancestry Group
Bilirubin
Cytochrome P-450 CYP1A1
Cytochrome P-450 CYP1A2*
Gene Frequency
Humans
Hyperbilirubinemia
Hyperbilirubinemia, Neonatal*
Incidence
Infant, Newborn*
Jaundice
Rats, Gunn
Risk Factors
Bilirubin
Cytochrome P-450 CYP1A1
Cytochrome P-450 CYP1A2