5. Biochemistry, molecular biology and molecular genetics of hyperbilirubinemia

Hyperbilirubinemia is the most common problem encountered in terms newborns which is mainly caused by abnormal liver function, hemolysis or genetic defect. Uncongugated bilirubin is produced mainly by the turnover of erythrocytes, after that it is transported by organic anion transporter polypeptide (OATP) to the liver, where uncongugated bilirubin is conjugated by uridine diphosphoglucuronate glucoronosyl transferase 1A1 (UGT1A1) before being excreted into the bile. The presence of mutations and polymorphism in UGT1A1 gene are associated with Crigler-Najjar and Gilbert syndrome. The Gilbert syndrome is an asymptomatic uncongugated hyperbilirubinemia that is most commonly caused by polymorphism in UGT1A1 gene worldwide. In Asian patients, the other mutations like G71R contribute significantly to hyperbilirubinemia, however this mutation was absent in Indian population in our study. Ala 72 Pro of exon 1 was found to be the most common mutation of UGT1A1 gene in our population. There is a spectrum of mutation in UGT1A1 gene that has been characterized worldwide which is associated with neonatal hyperbilirubinemia. In this context we characterized 21 mutations out of which 16 were novel mutations reported only in Indian population. The another gene which has been implicated in our study is OATP gene 6 mutations Correspondence/Reprint request: Prof. Rajendra Prasad, Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh -160012, India. E-mail: [email protected] Rajendra Prasad et al. 108 which was identified in 57 hyperbilirubinemic neonates, out of which 4 were novel. Another genetic defect, G6PD deficiency an X linked abnormality is the most commonly seen genetic defect affecting 400 million individuals worldwide. G6PD deficiency is also a known causative factor for hyperbilirubinemia. Most polymorphic mutations predominate in specific regions of the world: G6PD A(376G/202A) is prevalent in Africa and Southern Europe, G6PD Mediterranean (C563T) in Mediterranean countries, and G6PD Viangchan (G871A) in Asian countries. In our study we found Mediterranean and Orissa mutations to be most common.