Association of Neonatal Hyperbilirubinemia with UGT1A1 Gene Polymorphisms: A Meta-Analysis

Yu, Zibi; Zhu, Kaichang; Wang, Li; Liu, Ying; Sun, Jin

doi:10.12659/msm.894043

Cited by 19 publications

(6 citation statements)

References 52 publications

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“…Secondly, the collection of umbilical cord blood will provide valuable information otherwise rarely available on possible NH predisposing factors, such as the presence of a UGT1A1 polymorphisms (Gly71Arg and TATA promotor) associated with or without Gilbert’s and/or Crigler-Najjar syndrome [16], or Southeast Asian Ovalocytosis [17, 18]. …”

Section: Discussionmentioning

confidence: 99%

Neonatal Hyperbilirubinemia in a Marginalized Population on the Thai-Myanmar Border: a study protocol

et al. 2017

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BackgroundThis study aims to identify risk factors and the neurodevelopmental impact of neonatal hyperbilirubinemia in a limited-resource setting among a refugee and migrant population residing along the Thai-Myanmar border, an area with a high prevalence of glucose-6-phosphate dehydrogenase-deficiency.MethodsThis is an analytic, observational, prospective birth cohort study including all infants of estimated gestational age equal to or greater than 28 weeks from mothers who followed antenatal care in the Shoklo Malaria Research Unit clinics. At birth, a series of clinical exams and laboratory investigations on cord blood will be carried out. Serum bilirubin will be measured in all infants during their first week of life. All the infants of the cohort will be clinically followed until the age of one year, including monitoring of their neurodevelopment.DiscussionThe strength of this study is the prospective cohort design. It will allow us to collect information about the pregnancy and detect all infants with neonatal hyperbilirubinemia, to observe their clinical response under treatment and to compare their neurodevelopment with infants who did not develop neonatal hyperbilirubinemia. Our study design has some limitations in particular the generalizability of our findings will be limited to infants born after the gestational age of 28 weeks onwards and neurodevelopment to the end of the first year of life.Trial registrationClinicalTrials.gov ID NCT02361788, registration date September 1st, 2014.

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Section: Discussionmentioning

confidence: 99%

Neonatal Hyperbilirubinemia in a Marginalized Population on the Thai-Myanmar Border: a study protocol

et al. 2017

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“…Increased number of TA repeats in the promoter (UGT1A1 � 28; a common cause of Gilbert's syndrome) was found in 12% of the newborns and was associated with lower risk of NH. Two meta-analyses conducted in 2015 and 2020 [35,36] showed a large variability in risk of NH for each variant across the 34 included studies. Overall, the UGT1A1 � 6 allele was associated with a larger risk as compared to allele � 28 (the latter found mostly in African populations).…”

Section: Plos Global Public Healthmentioning

confidence: 99%

Contribution of genetic factors to high rates of neonatal hyperbilirubinaemia on the Thailand-Myanmar border

Bancone

Gornsawun

Peerawaranun

et al. 2022

PLOS Glob Public Health

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Very high unconjugated bilirubin plasma concentrations in neonates (neonatal hyperbilirubinaemia; NH) may cause neurologic damage (kernicterus). Both increased red blood cell turn-over and immaturity of hepatic glucuronidation contribute to neonatal hyperbilirubinaemia. The incidence of NH requiring phototherapy during the first week of life on the Thailand-Myanmar border is high (approximately 25%). On the Thailand-Myanmar border we investigated the contribution of genetic risk factors to high bilirubin levels in the first month of life in 1596 neonates enrolled in a prospective observational birth cohort study. Lower gestational age (<38 weeks), mutations in the genes encoding glucose-6-phosphate dehydrogenase (G6PD) and uridine 5′-diphospho-glucuronosyltransferase (UGT) 1A1 were identified as the main independent risk factors for NH in the first week, and for prolonged jaundice in the first month of life. Population attributable risks (PAR%) were 61.7% for lower gestational age, 22.9% for hemi or homozygous and 9.9% for heterozygous G6PD deficiency respectively, and 6.3% for UGT1A1*6 homozygosity. In neonates with an estimated gestational age ≥ 38 weeks, G6PD mutations contributed PARs of 38.1% and 23.6% for “early” (≤ 48 hours) and “late” (49–168 hours) NH respectively. For late NH, the PAR for UGT1A1*6 homozygosity was 7.7%. Maternal excess weight was also a significant risk factor for “early” NH while maternal mutations on the beta-globin gene, prolonged rupture of membranes, large haematomas and neonatal sepsis were risk factors for “late” NH. For prolonged jaundice during the first month of life, G6PD mutations and UGT1A1*6 mutation, together with lower gestational age at birth and presence of haematoma were significant risk factors. In this population, genetic factors contribute considerably to the high risk of NH. Diagnostic tools to identify G6PD deficiency at birth would facilitate early recognition of high risk cases.

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“…The meta-analysis of UGT1A1*6 studies in Southeast Asian populations including Malaysia and Thailand by Yu et al showed the same results of 0% A/A genotype frequency, which differed from other Asian populations such as India, Japan, and China. 16 In certain conditions with co-existing risk factors, UGT1A1*6 could still increase the risk for hyperbilirubinaemia. In one Japanese study, UGT1A1*6 was shown to be a cause of prolonged unconjugated hyperbilirubinaemia.…”

Section: Discussionmentioning

confidence: 99%

UGT1A1 gene polymorphisms and jaundice in Indonesian neonates

Rohsiswatmo¹,

Amandito

Putri³

et al. 2019

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Background Uridine diphospho-glucuronocyltransferase 1A1 (UGT1A1) polymorphisms are a risk factor for unconjugated hyperbilirubinemia in neonates. UGT1A1 polymorphisms decrease bilirubin conjugation, thus causing hyperbilirubinemia. A variety of polymorphisms have been reported, with UGT1A1*60 and UGT1A1*6 especially prominent in the Asian population. Hyperbilirubinemia polymorphism studies are lacking in Indonesian populations. Objective To identify UGT1A1*60 and UGT1A1*6 profiles in Indonesian populations of heterogeneous ethnicity. Methods We enrolled 42 jaundiced neonates who were born from January to April 2017 and treated in the Neonatal Intensive Care Unit of our national referral center, Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Genetic mutations *60 of exon 1 and *6 of the promoter region were analyzed by polymerase chain reaction – restriction fragment length polymorphism methods, with DraI and AvaII as restriction enzymes, respectively. Clinical data including total serum bilirubin and racial information were obtained by medical records and interviews with parents. Results There were no homozygous mutations of UGT1A1*6, but 4.8% of subjects were heterozygous. As for UGT1A1*60, 4.8% were heterozygous and 95.2% were homozygous. Racial variations were not observed for UGT1A1*60, while Betawi descendents were found to have many heteroygous forms of UGT1A1*6. Conclusion Polymorphisms of the UGT1A1 gene were found in Indonesian neonates. Some ethnicities also showed increased tendency towards its incidence, such as the heterozygous form of UGT1A1*6.

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Association of Neonatal Hyperbilirubinemia with UGT1A1 Gene Polymorphisms: A Meta-Analysis

Cited by 19 publications

References 52 publications

Neonatal Hyperbilirubinemia in a Marginalized Population on the Thai-Myanmar Border: a study protocol

Neonatal Hyperbilirubinemia in a Marginalized Population on the Thai-Myanmar Border: a study protocol

Contribution of genetic factors to high rates of neonatal hyperbilirubinaemia on the Thailand-Myanmar border

UGT1A1 gene polymorphisms and jaundice in Indonesian neonates

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