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Received Sep 10, 2017; Accepted Dec 4, 2017
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1. Introduction
Jaundice is a common physiological phenomenon in neonates as it occurs almost in 60% of healthy term newborns [1, 2]. Neonatal hyperbilirubinemia (NH) is a condition when jaundice with the serum total bilirubin (STB) levels is above the 95th percentile for age in hours [3]. In the most severe cases, NH leads to chronic bilirubin encephalopathy (kernicterus) which is characterized by severe athetoid cerebral palsy, sensory hearing loss, dental-enamel dysplasia, paralysis upward gaze, and mortality. Neonatal hyperbilirubinemia occurs due to the imbalance between production and elimination of bilirubin [2, 4]. One of the important processes in bilirubin elimination is glucuronic acid conjugation to bilirubin. Conjugated bilirubin is more polar and easier to eliminate compared to unconjugated bilirubin. The conjugation process occurs in the hepatocyte and is catalyzed by UDP-glucuronosyltransferase enzyme which is encoded by UGT1A1 gene [2, 4]. The prevalence of NH varies in different populations with the highest being in the Navajo Indian, Greek, and East Asian such as Japanese and Korean [4]. The previous study showed that the risk of experience hyperbilirubinemia is 12.5-fold higher than that in controls population if a previous sib had STB levels higher than 15 mg/dL [4, 5]. Furthermore, it has been reported that there was a high concordance of STB levels among identical twins in the European and Chinese. These findings suggest that a genetic component might contribute to the development of NH [4].
It has been reported that UGT1A1 rare and common variants were associated with NH in different populations [6–11]. It has been known also that UGT1A1 variants were underlying cause of prolonged unconjugated hyperbilirubinemia associated with breast milk in Japanese population [12]. These show that combination of genetic and nongenetic factors contributes to the development of the disease. More than 130 UGT1A1 variants have been reported causing Gilbert’s syndrome and Crigler-Najjar syndrome type 1 (CN1) and type 2 (CN2), which are characterized by inherited nonhemolytic unconjugated hyperbilirubinemia. The insertion of TA sequence in the TATAA box of the promoter region (TA7) had been...