Complex multifactorial nature of significant hyperbilirubinemia in neonates.

Abstract

OBJECTIVE:

To determine whether glucose-6-phosphate dehydrogenase (G6PD), uridine-diphosphoglucuronosyltransferase 1A1 (UGT1A1), and hepatic solute carrier organic anion transporter 1B1 (SLCO1B1) gene variants occur at greater frequency in neonates with significant hyperbilirubinemia.

METHODS:

Infants with gestational ages of >or=37 weeks and ages of <7 days were studied. Case subjects had >or=1 bilirubin level above the 95th percentile (high-risk zone), whereas control subjects had bilirubin levels of <40th percentile (low-risk zone) at study entry.

RESULTS:

A total of 153 case subjects (median bilirubin level: 15.7 mg/dL) and 299 control subjects (median bilirubin level: 4.6 mg/dL) were evaluated. There were no statistical differences in the frequencies of G6PD, UGT1A1, and SCLO1B1 gene variants between case and control subjects (G6PD: 5.2% vs 3.3%; UGT1A1: 14.4% vs 9.4%; SLCO1B1: 73.2% vs 73.6%). However, coexpression of the G6PD African A- mutation with UGT1A1 and/or SLCO1B1 variants was seen more frequently for case subjects. Case subjects more often demonstrated >or=2 factors contributing to hyperbilirubinemia, including ABO blood group heterospecificity in which the mother had blood group O (47.7% vs 11.4%), positive direct Coombs test results (33.3% vs 4%), sibling treated with phototherapy (16.3% vs 5.4%), maternal circulating blood group antibodies (10.5 vs 0.7%), maternal diabetes mellitus (13.1% vs 6.4%), and maternal East Asian ethnicity (6.5% vs 1.3%).

CONCLUSIONS:

Clinical contributors to hyperbilirubinemia were identified more frequently for case subjects but individually G6PD, UGT1A1, and SLCO1B1 variants were not. Coexpression of the G6PD African A- mutation with UGT1A1 and SLCO1B1 variants was seen more often for case subjects.

• Authors: Jon F Watchko, Zhili Lin, Reese H Clark, Amy S Kelleher, M Whit Walker, Alan R Spitzer, Pediatrix Hyperbilirubinemia Study Group
• Journal: Pediatrics (Pediatrics) Vol. 124 Issue 5 Pg. e868-77 (Nov 2009) ISSN: 1098-4275 [Electronic] United States
• PMID: 19858149 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Liver-Specific Organic Anion Transporter 1
• Organic Anion Transporters
• SLCO1B1 protein, human
• Glucosephosphate Dehydrogenase
• UGT1A1 enzyme
• Glucuronosyltransferase

Topics

• Female
• Gene Frequency
• Glucosephosphate Dehydrogenase (genetics)
• Glucuronosyltransferase (genetics)
• Humans
• Hyperbilirubinemia, Neonatal (etiology, genetics)
• Infant, Newborn
• Liver-Specific Organic Anion Transporter 1
• Male
• Mutation
• Organic Anion Transporters (genetics)
• Polymorphism, Genetic