Frequency of Two Common Variants in Hyperbilirubinemic Palestinian Patients رسالة ماجستير

Abstract

Elevated bilirubin levels are a common symptom of a condition known as neonatal hyperbilirubinemia (NH). While typically harmless, severe NH can lead to complications like bilirubin encephalopathy (kernicterus), causing brain damage. NH has both genetic and environmental risk factors. The UGT1A1 gene is essential for the metabolism of bilirubin because it encodes UDP-Glucuronosyl transferases, which are enzymes of the glucuronidation pathway that convert small lipophilic molecules like bilirubin into water soluble metabolites by conjugating bilirubin to glucuronic acid, which is necessary for excretion of bilirubin. Changes in bilirubin levels in different populations have been associated with variations in this gene. Certain syndromes characterized mainly by unconjugated hyperbilirubinemia are caused by different variants within the UGT1A1gene including Gilbert's syndrome (OMIM: 143500), Crigelr-Najjar type 1(OMIM: 218800), Crigler-Najjar type 2(OMIM:606785) and Transient familial neonatal hyperbilirubinemia (OMIM: 237900). The purpose of this study was to investigate the prevalence of two common variants within the UGT1A1 gene (rs3064744 [(TA)7TAA] and rs4124874 (c.-3279 T > G)) and their association with NH in Palestinian neonates. The study included 70 neonates diag nosed with NH ranging in age from 2 to 64 days. Genotyping was carried out using Sanger’s sequencing. Our analysis revealed an association between [(TA)7TAA] (rs3064744) variant and in creased bilirubin levels in the studied group. Moreover, while the c.-3279 T > G (rs4124874) variant was frequent among patients, it did not show a statistically significant correlation with NH. The study shows that there is a possible genetic contribution of variations in the UGT1A1 gene to elevated bilirubin levels in the Palestinian population. A better understanding of the genetic background of NH can improve personalized diagnostic and preventive strat egies, improving neonatal health outcomes in Palestine.