Dataset Information

UGT1A1 Genetic Variations and a Haplotype Associated with Neonatal Hyperbilirubinemia in Indonesian Population.

ABSTRACT: Neonatal hyperbilirubinemia (NH) is a common finding in newborn babies in Indonesia. Common and rare variants of UGT1A1 have been known to contribute to NH etiology. This study aims to identify UGT1A1 genetic variation and haplotype associated with NH in Indonesian population. DNA was isolated from 116 cases and 115 controls and a targeted-deep sequencing approach was performed on the promoter, UTRs, and exonic regions of UGT1A1. Determining association of common variants and haplotype analysis were performed using PLINK and Haploview. Ten and 4 rare variants were identified in cases and controls, respectively. The UGT1A1 rare variants frequency in cases (5.17%) was higher than that in controls (1.7%). Four of those rare variants in cases (p.Ala61Thr, p.His300Arg, p.Lys407Asn, and p.Tyr514Asn) and three in controls (p.Tyr79X, p.Ala346Val, and p.Thr412Ser) are novel variants. The frequencies of p.Gly71Arg, p.Pro229Gln, and TA7 common variants were not significantly different between cases and controls. A haplotype, consisting of 3 major alleles of 3' UTRs common variants (rs8330C>G, rs10929303C>T, and rs1042640C>G), was associated with NH incidence (p = 0.025) in this population. Using targeted-deep sequencing and haplotype analysis, we identified novel UGT1A1 rare variants and disease-associated haplotype in NH in Indonesian population.

SUBMITTER: Wisnumurti DA

PROVIDER: S-EPMC5828093 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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UGT1A1 Genetic Variations and a Haplotype Associated with Neonatal Hyperbilirubinemia in Indonesian Population.

Wisnumurti Dewi A DA Sribudiani Yunia Y Porsch Robert M RM Maskoen Ani M AM Abdulhamied Lola I LI Rahayuningsih Sri E SE Asni Eni K EK Sleutels Frank F Kockx Christel E M CEM van Ijcken Wilfred F J WFJ Sukadi Abdurachman A Achmad Tri H TH

BioMed research international 20180123

Neonatal hyperbilirubinemia (NH) is a common finding in newborn babies in Indonesia. Common and rare variants of UGT1A1 have been known to contribute to NH etiology. This study aims to identify UGT1A1 genetic variation and haplotype associated with NH in Indonesian population. DNA was isolated from 116 cases and 115 controls and a targeted-deep sequencing approach was performed on the promoter, UTRs, and exonic regions of UGT1A1. Determining association of common variants an ...[more]

PMID: 29607327

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Project description:BackgroundNeonatal jaundice is a common finding in newborns in Asia, including Indonesia. In some cases, the serum total bilirubin levels exceeds the 95th percentile for hours of life (neonatal hyperbilirubinemia). Severe neonatal hyperbilirubinemia (NH) could lead to kernicterus and neonatal death. Glucose-6-Phosphage Dehydrogenase (G6PD) genetic variations and deficiency have been reported in several studies to be associated with NH. This study aimed to analyze the G6PD genetic variations and its activity in neonates with and without hyperbilirubinemia in the Deutromalay Indonesian population.MethodsDeoxyribose Nucleic Acid (DNA) was isolated from peripheral blood of 116 and 115 healthy term neonates with and without hyperbilirubinemia. All infants underwent the following laboratory examinations: routine hematologic evaluation, Coombs test, G6PD activity measurement using the Randox kit method, and serum total bilirubin level. All exons of the G6PD gene were targeted for deep sequencing using MiSeq (Illumina). An association study of G6PD polymorphisms with NH was performed using PLINK.ResultsThe prevalence of G6PD deficiency in neonates with and without hyperbilirubinemia in Indonesian Deutromalay population were 1.72% (95% Confidence Interval (CI): 0.6-4.1%) and 1.74% (95% CI: 0.7-4.1%), respectively. The most common G6PD polymorphisms, i.e. rs1050757/c.* + 357A > G, rs2230037/c.1311C > T, and rs2071429/c.1365-13 T/IVS11, were identified. However, none of those polymorphisms and their haplotype were associated with NH (p > 0.05, Odds Ratio (OR) ~1.00). The prevalence of G6PD mutations in neonates with and without hyperbilirubinemia were 6.8% (95% CI: 2.3-11.5%) and 6.9% (95% CI: 2.3-11.6%), respectively. The most frequently identified G6PD mutation was the Viangchan variant (p.V291 M), which was followed by the Canton (p.R459L) and Vanua Lava (p.L128P) variants. Two novel mutations were identified both in case (p.V369A, p.I167F) and control (p.L474=, p.I36T) groups.ConclusionThe prevalence of G6PD deficiency is low in neonates with or without hyperbilirubinemia in Deutromalay Indonesian population. The majority of G6PD mutations identified among Indonesian Deutromalay population in this study are Viangchan, Canton and Vanua Lava variants.

Dataset Information

UGT1A1 Genetic Variations and a Haplotype Associated with Neonatal Hyperbilirubinemia in Indonesian Population.

Publications

<i>UGT1A1</i> Genetic Variations and a Haplotype Associated with Neonatal Hyperbilirubinemia in Indonesian Population.

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