The role of UGT1A1 (c.-3279 T &gt; G) gene polymorphisms in neonatal hyperbilirubinemia susceptibility

Li, Zijin; Song, Li; Hao, Lihong

doi:10.1186/s12881-020-01155-2

Cited by 8 publications

(4 citation statements)

References 31 publications

(38 reference statements)

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“…Other genetic traits not analysed here presumably contributed to increased risk. Other UGT1A1 variants associated to increased risk in Asian population [43] have not been investigated here. Variation in expression of the HMOX gene which encodes for heme oxygenase, the enzyme responsible for transformation of heme into biliverdin, has been shown to be associated with increased risk of NH [38].…”

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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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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“…Severe hyperbilirubinemia may cause bilirubin encephalopathy and kernicterus and can result in hearing loss, cerebral palsy and disorders of mental development[ 1 ]. The importance of genetic contributions in neonatal jaundice has been recognized in recent years[ 2 - 5 ]. We previously demonstrated that the genetic polymorphisms of uridine diphosphate glucuronosyltransferase 1A1 ( UGT1A1 ), solute carrier organic anion transporter family member 1B1 ( SLCO1B1 ), SLCO1B3 and glucose-6-phosphate dehydrogenase ( G6PD ) contributed to an increased risk of neonatal hyperbilirubinemia, which reflected the complexity of pathological jaundice[ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical features and genetic variations of severe neonatal hyperbilirubinemia: Five case reports

Lin¹,

Xu²,

Wu³

et al. 2022

WJCC

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BACKGROUND Neonatal hyperbilirubinemia is a common problem faced by pediatricians. The role of genetic factors in neonatal jaundice has been gradually recognized. This study aims to identify genetic variants that influence the bilirubin level in five patients using next-generation sequencing (NGS). CASE SUMMARY Five neonates with severe hyperbilirubinemia were retrospectively studied. They exhibited bilirubin encephalopathy, hypothyroidism, ABO blood type incompatibility hemolysis, glucose-6-phosphate dehydrogenase ( G6PD ) deficiency and premature birth, respectively. A customized 22-gene panel was designed, and NGS was carried out for these neonates. Eight variations ( G6PD c.G1388A, HBA2 c.C369G, ABCC2 c.C3825G, UGT1A1 c.G211A, SPTB c.A1729G, EPB41 c.G520A, c.1213-4T>G and c.A1474G) were identified in these five neonates. Genetic mutations of these genes are associated with G6PD deficiency, thalassemia, Dubin-Johnson syndrome, Gilbert syndrome, hereditary spherocytosis, and hereditary elliptocytosis. One of the neonates was found to have compound variants of the EPB41 splice site c.1213-4T>G and c.G520A (p.E174K), but no elliptocyte was seen on his blood smear of 4 years old. CONCLUSION Pathological factors of severe neonatal hyperbilirubinemia are complicated. Genetic variants may play an important role in an increased risk of neonatal hyperbilirubinemia, and severe jaundice in neonates may be related to a cumulative effect of genetic variants.

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“…As for the UGT1A7 gene, rs11692021 polymorphism was related to higher risk of chronic pancreatitis (aOR = 1.76, 95% CI: 1.26–2.46) [ 30 ]. In addition, rs4124874 and rs4148323 polymorphism were associated with in increased risk of hyperbilirubinemia [ 31 , 32 ]. However, rs887829 genotype was related to a decreased risk of hyperbilirubinemia (aOR = 0.55, 95% CI: 0.34–0.89) [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control study

Li,

Kang,

Liu

et al. 2024

BMC Pregnancy Childbirth

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Background The majority of congenital heart diseases (CHDs) are thought to result from the interactions of genetics and the environment factors. This study aimed to assess the association of maternal non-occupational phthalates exposure, metabolic gene polymorphisms and their interactions with risk of CHDs in offspring. Methods A multicenter case-control study of 245 mothers with CHDs infants and 268 control mothers of health infant was conducted from six hospitals. Maternal urinary concentrations of eight phthalate metabolites were measured by ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Twenty single nucleotide polymorphisms (SNPs) in cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and 19 (CYP2C19), uridine diphosphate (UDP) glucuronosyl transferase family 1 member A7 (UGT1A7), family 2 member B7 (UGT2B7) and B15(UGT2B15) genes were genotyped. The multivariate logistic regressions were used to estimate the association between maternal phthalates exposure or gene polymorphisms and risk of CHDs. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene–gene and gene–phthalates exposure interactions. Results There was no significant difference in phthalate metabolites concentrations between the cases and controls. No significant positive associations were observed between maternal exposure to phthalates and CHDs. The SNPs of UGT1A7 gene at rs4124874 (under three models, log-additive: aOR = 1.74, 95% CI:1.28–2.37; dominant: aOR = 1.86, 95% CI:1.25–2.78; recessive: aOR = 2.50, 95% CI: 1.26–4.94) and rs887829 (under the recessive model: aOR = 13.66, 95% CI: 1.54–121) were significantly associated with an increased risk of CHDs. Furthermore, the associations between rs4124874 (under log-additive and dominant models) of UGT1A7 were statistically significant after the false discovery rate correction. No significant gene-gene or gene-phthalate metabolites interactions were observed. Conclusions The polymorphisms of maternal UGT1A7 gene at rs4124874 and rs887829 were significantly associated with an increased risk of CHDs. More large-scale studies or prospective study designs are needed to confirm or refute our findings in the future.

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The role of UGT1A1 (c.-3279 T > G) gene polymorphisms in neonatal hyperbilirubinemia susceptibility

Cited by 8 publications

References 31 publications

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

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

Clinical features and genetic variations of severe neonatal hyperbilirubinemia: Five case reports

Association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control study

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