Presence of the genetic marker for Gilbert syndrome is associated with increased level and duration of neonatal jaundice

Roy‐Chowdhury, Namita; Deocharan, Bisram; Bejjanki, HR; Roy‐Chowdhury, Jayanta; Koliopoulos, C; Petmezaki, Sophia; Valaes, Timos

doi:10.1111/j.1651-2227.2002.tb01650.x

Cited by 41 publications

(13 citation statements)

References 5 publications

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“…18,30,31 Two studies have found that UGT1A1*28 contributed to prolonged neonatal jaundice. 32,33 Thus, our primary outcome is consistent with most of the previous findings.…”

Section: Strengths and Limitationssupporting

confidence: 82%

Extreme Neonatal Hyperbilirubinemia and a Specific Genotype: A Population-Based Case-Control Study

Petersen

Henriksen²,

Hollegaard

et al. 2014

Pediatrics

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WHAT'S KNOWN ON THIS SUBJECT: For newborn infants, extreme hyperbilirubinemia ($24.5 mg/dL) is associated with risk for severe bilirubin encephalopathy. The causal factor of extreme hyperbilirubinemia is often not established. The genotype of Gilbert syndrome, the UGT1A1*28 allele, is considered a potential risk factor. WHAT THIS STUDY ADDS:The UGT1A1*28 allele was not associated with risk for developing extreme hyperbilirubinemia. abstract OBJECTIVES: Extreme hyperbilirubinemia (plasma bilirubin $24.5 mg/dL) is an important risk factor for severe bilirubin encephalopathy. Several risk factors for hyperbilirubinemia are known, but in a large number of patients, a causal factor is never established. UGT1A1 is the rate-limiting enzyme in bilirubin' s metabolism. The genotype of Gilbert syndrome, the UGT1A1*28 allele, causes markedly reduced activity of this enzyme, but its association with neonatal hyperbilirubinemia is uncertain and its relationship with extreme hyperbilirubinemia has not been studied. We examined whether the UGT1A1*28 allele is associated with extreme hyperbilirubinemia. METHODS:The UGT1A1*28 allele was assessed in a case-control study of 231 white infants who had extreme hyperbilirubinemia in Denmark from 2000 to 2007 and 432 white controls. Cases were identified in the Danish Extreme Hyperbilirubinemia Database that covers the entire population. Genotypes were obtained through the Danish Neonatal Screening Biobank. Subgroup analysis was done for AB0 incompatible cases. RESULTS:No association was found between the UGT1A1*28 allele and extreme hyperbilirubinemia. With the common genotype as reference, the odds ratio of extreme hyperbilirubinemia was 0.87 (range, 0.68-1.13) for UGT1A1*28 heterozygotes and 0.77 (range, 0.46-1.27) for homozygotes. Also, no association was found for AB0 incompatible cases.

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“…18,30,31 Two studies have found that UGT1A1*28 contributed to prolonged neonatal jaundice. 32,33 Thus, our primary outcome is consistent with most of the previous findings.…”

Section: Strengths and Limitationssupporting

confidence: 82%

Extreme Neonatal Hyperbilirubinemia and a Specific Genotype: A Population-Based Case-Control Study

Petersen

Henriksen²,

Hollegaard

et al. 2014

Pediatrics

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“…Bancroft et al (28) who measured transcutaneous bilirubin index in first 2 d of life and Roy-Chowdhury et al (29)who measured STB values at 96 h of life found higher values of STB in neonates homozygous for the variant (TA) 7 promoter compared with homozygous normal (TA) 6 controls. The onset of jaundice and peak STB values in the various genotype groups in our study was not different statistically.…”

Section: Discussionmentioning

confidence: 99%

UGT1A1 Gene Polymorphisms in North Indian Neonates Presenting with Unconjugated Hyperbilirubinemia

et al. 2009

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Genetic factors are implicated in pathogenesis of neonatal hyperbilirubinemia. In this nested case-control study, we determined 1) frequency of thymine-adenine (TA) n promoter polymorphism and Gly71Arg mutation in uridine diphosphoglucuronateglucuronosyltransferase 1A1 (UGT1A1) gene in neonates Ն35-wk gestation presenting with bilirubin levels Ն18 mg/dL and controls, 2) interaction among (TA) n promoter polymorphism, glucose-6-phosphate dehydrogenase (G6PD) gene mutations, and peak bilirubin. The number of TA repeats was assessed by PCR-single-strand conformation polymorphism (SSCP) analysis and Gly71Arg mutation by PCR-RFLP. Fifty samples of both mutations were verified with DNA sequencing. One hundred twenty-seven neonates were enrolled (77 hyperbilirubinemics, 50 controls). The incidence of (TA) n polymorphism was higher in babies with hyperbilirubinemia [89.6% vs. 50%, OR 8.63 (95% CI, 3.2-24.1)]. Gly71Arg mutation was not found either in hyperbilirubinemics or controls. A novel polymorphism (Ala72Pro) at codon position 72 of exon 1 was detected in all 50 samples (21 hyperbilirubinemics, 29 controls), which were sequenced. Presence of variant (TA) n promoter (adjusted OR, 10.6; 95% CI, 3.3-34.2), G6PD deficiency (adjusted OR, 20.6; 95% CI, 3.6 -117.3), and history of jaundice in sibling requiring phototherapy (adjusted OR, 12.6; 95% CI, 1.1-141.6) were independent risk factors for bilirubin levels Ն18 mg/dL. (Pediatr Res 65: 675-680, 2009) T he incidence and severity of neonatal hyperbilirubinemia is significantly higher in Asians, more so in North Indians, than in Caucasians (1,2). Despite all standard investigations, no cause is identified in 48 -58% of these cases (2,3). Genetic factors have been implicated in such situations; however, their contribution in Indian population has not been reported. Genetic variants involving red blood cell enzyme glucose-6-phosphate dehydrogenase (EC 1.1.1.49; G6PD) and bilirubin conjugating enzyme uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (EC 2.4.1.17; UGT1A1) have been commonly associated with neonatal hyperbilirubinemia (4,5). The usual polymorphism described in Caucasians is additional thymine-adenine (TA) insertions in the normal sequence A(TA) 6 TAA of the TATAA box promoter of the UGT1A1 gene (6). However, in East Asians, missence mutations in the coding area of the UGT1A1 gene, especially G3 A transition at nucleotide position 211 of exon 1 (Gly71Arg) are the most common (7). The types, prevalence, and importance of various mutations of UGT1A1 gene vary across different regions of world.Hence, this study was conducted with the primary objective of determining the frequency of (TA) n promoter polymorphism and Gly71Arg mutation in the UGT1A1 gene in North Indian neonates Ն35-wk gestation presenting with serum total bilirubin (STB) Ն18 mg/dL. The secondary objective was to study the interaction among the presence of UGT1A1 gene polymorphisms, G6PD gene mutations, and peak STB levels. PATIENTS AND METHODSThis was a hospital-based nested case-co...

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“…Indeed, (TA)7 insertion is the most common mutation causing Gilbert syndrome in Caucasians (6,7), and multiple studies have revealed its relationship with neonatal hyperbilirubinemia in Caucasians (14,(24)(25)(26)(27)(28)(29)(30). Roy-Chowdhury et al (24) reported that the (TA)7 allele may be associated with high TSB levels. Agrawal et al (14) reported that (TA)n promoter variations are significantly associated with neonatal hyperbilirubinemia in North India.…”

Section: Articlesmentioning

confidence: 99%

UGT1A1 gene mutations and neonatal hyperbilirubinemia in Guangxi Heiyi Zhuang and Han populations

Zhong

Xie

et al. 2015

Pediatr Res

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Articles Population Study nature publishing groupBackground: Uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene mutation was shown to be responsible for neonatal hyperbilirubinemia. This study aimed to investigate whether UGT1A1 gene mutation is associated with neonatal hyperbilirubinemia in Guangxi Heiyi Zhuang and Han populations. Methods: Two hundred and eighteen infants with hyperbilirubinemia (118 Heiyi Zhuang, 100 Han) and 190 control subjects (110 Heiyi Zhuang, 80 Han) were enrolled. Polymerase chain reaction and gene sequencing were used to detect the TATA-box and exon 1 of UGT1A1. results: (TA)7 insertion mutation, 211G>A (G71R), 686C>A (P229Q), and 189C>T (D63D) were detected. Logistic regression analysis showed odds ratios (OR) of 2.64 (95% confidence interval (CI) 1.64-4.24; P < 0.001) and 0.69 (95%CI 0.43-1.10; P = 0.115) for neonates who carried UGT1A1 G71R and (TA)7 insertion mutation, respectively. G71R homozygosity increased the odds of dangerous bilirubin levels by a factor 34.23, and G71R heterozygosity only by 2.10. conclusion: We found that UGT1A1 G71R mutation is a risk factor for neonatal hyperbilirubinemia in Guangxi Heiyi Zhuang and Han populations. Meanwhile, the UGT1A1 (TA)7 insertion mutation is not associated with neonatal hyperbilirubinemia in the two ethnic groups.

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Presence of the genetic marker for Gilbert syndrome is associated with increased level and duration of neonatal jaundice

Cited by 41 publications

References 5 publications

Extreme Neonatal Hyperbilirubinemia and a Specific Genotype: A Population-Based Case-Control Study

Extreme Neonatal Hyperbilirubinemia and a Specific Genotype: A Population-Based Case-Control Study

UGT1A1 Gene Polymorphisms in North Indian Neonates Presenting with Unconjugated Hyperbilirubinemia

UGT1A1 gene mutations and neonatal hyperbilirubinemia in Guangxi Heiyi Zhuang and Han populations

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