title: High resolution melting analysis of the NR1I3 genetic variants: Is there an association with neonatal hyperbilirubinemia?
abstract: Constitutive androstane receptor (CAR) encoded by the nuclear receptor subfamily 1, group I, member 3 (NR1I3) gene regulates the elimination of bilirubin through activating the components of the bilirubin clearance pathway. Hence, NR1I3 genetic variants may affect bilirubin metabolism and result in neonatal hyperbilirubinemia. Thus far, research which investigates the association between NR1I3 variants and neonatal hyperbilirubinemia has not been undertaken in any population. The present study aimed to evaluate the influence of MPJ6_1I3008 (rs10157822), IVS8+116T>G (rs4073054) and 540A>G (rs2307424) on neonatal hyperbilirubinemia development in the Malay population. Buccal swabs were collected from 232 hyperbilirubinemia and 277 control term newborns with gestational age ≥37weeks and birth weight ≥2500g. The NR1I3 variants were genotyped by using high resolution melting (HRM) assays and verified by DNA sequencing. Gender, mode of delivery and birth weight did not differ between hyperbilirubinemia and control groups. The genotypic and allelic frequencies of MPJ6_1I3008, IVS8+116T>G and 540A>G were not significantly different between the groups. However, stratification by gender revealed a significant inverse association between homozygous variant genotype of MPJ6_1I3008 and risk of neonatal hyperbilirubinemia in the females (OR, 0.44; 95% CI, 0.20-0.95; p=0.034). This study demonstrates that the homozygous variant genotype of MPJ6_1I3008 was associated with a significant reduced risk of neonatal hyperbilirubinemia in the females.
authors.affiliation: Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia, Kelantan 16150, Malaysia.
authors.forename: Tian Pei
authors.initials: TP
authors.lastname: Cheung
authors.affiliation: Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia, Kelantan 16150, Malaysia.
authors.forename: Hans
authors.initials: H
authors.lastname: Van Rostenberghe
authors.affiliation: Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia, Kelantan 16150, Malaysia.
authors.forename: Rosliza
authors.initials: R
authors.lastname: Ismail
authors.affiliation: Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia, Kelantan 16150, Malaysia.
authors.forename: Noor Namirah
authors.initials: NN
authors.lastname: Nawawi
authors.affiliation: Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia, Kelantan 16150, Malaysia.
authors.forename: Nurul Amierah
authors.initials: NA
authors.lastname: Abdullah
authors.affiliation: Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia, Kelantan 16150, Malaysia.
authors.forename: Noraida
authors.initials: N
authors.lastname: Ramli
authors.affiliation: Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia, Kelantan 16150, Malaysia.
authors.forename: Nor Rosidah
authors.initials: NR
authors.lastname: Ibrahim
authors.affiliation: Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia, Kelantan 16150, Malaysia.
authors.forename: Noorizan
authors.initials: N
authors.lastname: Hj Abd Majid
authors.affiliation: Advanced Medical and Dental Institute, Universiti Sains Malaysia, Pulau Pinang 11800, Malaysia.
authors.forename: Narazah
authors.initials: N
authors.lastname: Mohd Yusoff
authors.affiliation: Department of Pediatrics, Department of Community Medicine and Social Healthcare Science, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Hisahide
authors.initials: H
authors.lastname: Nishio
authors.affiliation: Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia, Kelantan 16150, Malaysia; Human Genome Center, School of Medical Sciences, Universiti Sains Malaysia, Kelantan 16150, Malaysia. Electronic address: surini@usm.my.
authors.forename: Surini
authors.initials: S
authors.lastname: Yusoff
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D000090702:Constitutive Androstane Receptor; D003430:Cross-Sectional Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006239:Haplotypes; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D065840:Protective Factors; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012727:Sex Characteristics; D044366:Transition Temperature
chemical_list: D000090702:Constitutive Androstane Receptor; C000716327:NR1I3 protein, human; D018160:Receptors, Cytoplasmic and Nuclear
keywords: Buccal; Constitutive androstane receptor; High resolution melting; Hyperbilirubinemia; Malay; Neonatal jaundice