Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

Does heterozygosity for UGT1A1 *28 convey increased risk for severe neonatal jaundice?

Journal of Perinatology volume 41, pages 658–660 (2021)Cite this article

Subjects

UDP-Glycosyltransferase 1 family, polypeptide A1 (UGT1A1) encodes the critically important bilirubin glucuronosyltransferase. Certain polymorphisms in the UGT1A1 promotor will retard bilirubin conjugation, leading to unconjugated hyperbilirubinemia. The most common example, Gilbert’s syndrome (OMIM # 143500), affects three to ten percent of the general population and can result in neonatal hyperbilirubinemia, typically of only moderate severity [1]. The usual polymorphism causing Gilbert’s syndrome is termed “UGT1A1 *28” and is an additional TA repeat in the TATA box of the promotor, resulting in A(TA)7TAA rather than the normal A(TA)6TAA. This form of Gilbert’s syndrome requires the presence of a *28 variant on both UGT1A1 promotor alleles, thus the inheritance is autosomal recessive. When a heterozygous UGT1A1 *28 state is identified in a neonate, it is generally interpreted as benign or minimally pathogenic [1].

Herein we present information challenging that interpretation, and leading us to posit that, under certain conditions, heterozygosity for *28 in a neonate can indeed be a significant contributor to hyperbilirubinemia. We offer three supporting arguments; two from the literature and one from our own recent and previously unpublished data.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra BA, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s syndrome. N Engl J Med. 1995;333:1171–5.

    Article  CAS  Google Scholar 

  2. Riera P, Salazar J, Virgili AC, Tobeña M, Sebio A, Gallano P, et al. Relevance of CYP3A4*20, UGT1A1*37 and UGT1A1*28 variants in irinotecan-induced severe toxicity. Br J Clin Pharmacol. 2018;84:1389–92.

    Article  CAS  Google Scholar 

  3. Kaplan M, Beutler E, Vreman HJ, Hammerman C, Levy-Lahad E, Renbaum P, et al. Neonatal hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient heterozygotes. Pediatrics. 1999;104:68–74.

    Article  CAS  Google Scholar 

  4. Zangen S, Kidron D, Gelbart T, Roy-Chowdhury N, Wang X, Kaplan M. Fatal kernicterus in a girl deficient in glucose-6-phosphate dehydrogenase: a paradigm of synergistic heterozygosity. J Pediatr. 2009;154:616–9.

    Article  Google Scholar 

  5. Roy-Chowdhury N, Deocharan B, Bejjanki HR, Roy-Chowdhury J, Koliopoulos C, Petmezaki S, et al. Presence of the genetic marker for Gilbert syndrome is associated with increased level and duration of neonatal jaundice. Acta Paediatr. 2002;91:100–2.

    Article  CAS  Google Scholar 

  6. Bahr TM, Christensen RD, Agarwal AM, George TI, Bhutani VK. The neonatal acute bilirubin encephalopathy registry (NABER): background, aims, and protocol. Neonatology. 2019;115:242–6.

    Article  CAS  Google Scholar 

  7. Rets A, Clayton AL, Christensen RD, Agarwal AM. Molecular diagnostic update in hereditary hemolytic anemia and neonatal hyperbilirubinemia. Int J Lab Hematol. 2019;41:95–101.

    Article  Google Scholar 

  8. 1000 Genomes Project Consortium, Auton A, Brooks LD, et al. A global reference for human genetic variation. Nature. 2015;526:68–74.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, University of Utah Health, Salt Lake City, UT, USA

    Timothy M. Bahr & Robert D. Christensen

  2. Division of Hematopathology, Department of Pathology, University of Utah Health and ARUP Laboratories, Salt Lake City, UT, USA

    Archana M. Agarwal

  3. Division of Hematology/Oncology, Department of Pediatrics, University of Utah Health, Salt Lake City, UT, USA

    Robert D. Christensen

Authors
  1. Timothy M. Bahr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Archana M. Agarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert D. Christensen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Timothy M. Bahr.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bahr, T.M., Agarwal, A.M. & Christensen, R.D. Does heterozygosity for UGT1A1 *28 convey increased risk for severe neonatal jaundice?. J Perinatol 41, 658–660 (2021). https://doi.org/10.1038/s41372-020-00826-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-020-00826-5

Search

Advanced search

Quick links