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GENERAL COMMENTARY article

Front. Pediatr., 07 February 2020
Sec. Neonatology

Commentary: Profiling of UGT1A1*6, UGT1A1*60, UGT1A1*93, and UGT1A1*28 Polymorphisms in Indonesian Neonates With Hyperbilirubinemia Using Multiplex PCR Sequencing

\nMohammad Reza Heydari
Mohammad Reza Heydari1*Majid FardaeiMajid Fardaei2
  • 1Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
  • 2Department of Medical Genetic, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran

A Commentary on
Profiling of UGT1A1*6, UGT1A1*60, UGT1A1*93, and UGT1A1*28 Polymorphisms in Indonesian Neonates With Hyperbilirubinemia Using Multiplex PCR Sequencing

by Amandito, R., Rohsiswatmo, R., Carolina, E., Maulida, R., Kresnawati, W., and Malik, A. (2019). Front. Pediatr. 7:328. doi: 10.3389/fped.2019.00328

Neonatal hyperbilirubinemia is a common benign phenomenon, related to a variety of physiological, pathological, and genetic conditions of neonates (1). Since this disorder can lead to neurodevelopmental impairment, finding the predictable factors could guide clinicians to provide better care (2). We read this article by Amandito et al. and congratulate the authors and also provide some suggestions.

In this well-designed cross-sectional study, the genetic sequencing was fully performed in different parts of the UGT1A1 gene, which is related to Gilbert syndrome (3). Finally, the researchers made an attempt to create a link between a neonate's genetic map with his/her bilirubin level. In this study, four polymorphisms in the UGT1A1 gene were investigated. By paying attention to the location of the single nucleotide polymorphisms, at least two genes UGT1A1*60(−3279T>G) and UGT1A1*6(−3156G>A) are situated in very close proximity (4).

An important concept in genetic polymorphism is linkage disequilibrium. It means that two genes are physically linked to each other, and alleles do not occur randomly with respect to each other (5).

In conclusion, due to the high likelihood of these two mutations moving together (6), the researchers have to calculate the linkage disequilibrium value before performing the statistical tests. If the D′ value was high, in their analysis, two mutations were considered as one. For this reason, they have to decide to test this mutation together either or alone.

Author Contributions

All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

1. Zhou Y, Wang S-N, Li H, Zha W, Wang X, Liu Y, et al. Association of UGT1A1 variants and hyperbilirubinemia in breast-fed full-term Chinese infants. PLoS ONE. (2014) 9:e104251. doi: 10.1371/journal.pone.0104251

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2. Alkén J, Håkansson S, Ekéus C, Gustafson P, Norman M. Rates of extreme neonatal hyperbilirubinemia and kernicterus in children and adherence to national guidelines for screening, diagnosis, and treatment in Sweden. JAMA Netw Open. (2019) 2:e190858. doi: 10.1001/jamanetworkopen.2019.0858

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3. Amandito R, Rohsiswatmo R, Carolina E, Maulida R, Kresnawati W, Malik A. Profiling of UGT1A1*6, UGT1A1*60, UGT1A1*93, and UGT1A1*28 polymorphisms in indonesian neonates with hyperbilirubinemia using multiplex PCR sequencing. Front Pediatr. (2019) 7:328. doi: 10.3389/fped.2019.00328

PubMed Abstract | CrossRef Full Text | Google Scholar

4. Heydari MR, Fardaei M, Kadivar MR, Rezaianzadeh A, Panjehshahin MR, Bardeji ZG, et al. Development of biliary and renal stone and sludge after taking Ceftriaxone is associated with a defect in UDP-Glucuronosyltransferase (ie Gilbert's syndrome). GastroHep. (2019) 1:55–60. doi: 10.1002/ygh2.326

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5. Goode EL. Linkage Disequilibrium. In: Schwab M, editor. Encyclopedia of Cancer. Berlin; Heidelberg: Springer (2011). p. 2043–8. doi: 10.1007/978-3-642-16483-5_3368

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6. Choi JR, Kim J, Kang DR, Kim IK, Chae HS, Kang JH. Haplotypes of UGT1A1 and total bilirubin concentration. J Health Info Stat. (2012) 37:46–57.

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Keywords: linkage disequilibrium, hyperbilirubinemia, neonatal, UGT1A1 enzyme, Gilbert disease

Citation: Heydari MR and Fardaei M (2020) Commentary: Profiling of UGT1A1*6, UGT1A1*60, UGT1A1*93, and UGT1A1*28 Polymorphisms in Indonesian Neonates With Hyperbilirubinemia Using Multiplex PCR Sequencing. Front. Pediatr. 7:528. doi: 10.3389/fped.2019.00528

Received: 26 September 2019; Accepted: 05 December 2019;
Published: 07 February 2020.

Edited by:

Arjan Te Pas, Leiden University, Netherlands

Reviewed by:

Ronald James Wong, Stanford University, United States
Kazumichi Fujioka, Kobe University, Japan

Copyright © 2020 Heydari and Fardaei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Mohammadreza Heydari, heydari280@yahoo.com

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.