Published online June 16, 2008
PEDIATRICS Vol. 122 No. 1 July 2008, pp. e156-e162 (doi:10.1542/10.1542/peds.2007-3249)
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lin, Z.
Right arrow Articles by Watchko, J. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lin, Z.
Right arrow Articles by Watchko, J. F.
Related Collections
Right arrow Gastrointestinal Tract
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

ARTICLE

Coexpression of Gene Polymorphisms Involved in Bilirubin Production and Metabolism

Zhili Lin, PhDa, Jamie Fontaine, BSa and Jon F. Watchko, MDb

a Pediatrix Screening, Inc, Bridgeville, Pennsylvania
b Division of Newborn Medicine, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

OBJECTIVE. The potential for genetically determined conditions to modulate the risk for developing neonatal hyperbilirubinemia is increasingly being recognized. The aims of this investigation were to (1) develop genotyping assays for an expanded panel of mutations and polymorphisms across 3 genes that are involved in bilirubin production and metabolism (glucose-6-phosphate dehydrogenase [G6PD], uridine diphosphate glucuronosyl transferase 1A1 [UGT1A1], and organic anion transporter polypeptide 1B1 [OATP1B1]) and (2) determine their allele frequencies in 450 anonymous DNA samples of US residents with ancestry from all of the major regions of the world.

METHODS. Genotyping assays were developed on the basis of allele-specific hybridization and melting peak analysis of the probe set and the match or mismatch template. Allele frequencies and the complexity of coinheritance of multiple genetic variants across G6PD, UGT1A1, and OATP1B1 genes in DNA samples from the DNA Polymorphism Discovery Resource of the National Human Genome Research Institute were determined by using this expanded panel.

RESULTS. Genetic polymorphisms of the UGT1A1 promoter, specifically the T-3279G phenobarbital responsive enhancer module and the (thymidine-adenine)7 dinucleotide repeat TATAA box variants, were common. Similarly, OATP1B1 coding sequence gene variants were frequently observed. Moreover, in more than three quarters of the samples, ≥2 variants were detected, reflecting a high degree of polymorphism coexpression across these genes, including those who carried the African A– G6PD mutation.

CONCLUSIONS. We conclude that this expanded panel of mutations and polymorphisms can serve as an effective instrument to study the genetic architecture of hyperbilirubinemia and speculate an important role for genetic polymorphism coinheritance in determining hyperbilirubinemia risk in newborns.

Key Words: genetics • glucose-6-phosphate dehydrogenase • hyperbilirubinemia • organic anion transporter polypeptide 1B1 • uridine diphosphate glucuronosyl transferase 1A1 • phenobarbital responsive enhancer module

Abbreviations: G6PD—glucose-6-phosphate dehydrogenase • UGT1A1—uridine diphosphate glucuronosyl transferase 1A1 • OATP1B1—organic anion transporter polypeptide 1B1 • PBREM—phenobarbital responsive enhancer module • PCR—polymerase chain reaction

Accepted Jan 9, 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?