We develop a strategy for haplotype analysis of PCR products that contained two adjacent heterozygous loci using sequencing with specific primers, allele-specific primers, and ddNTP-blocked primers. To validate its feasibility, two sets of PCR products, including two adjacent heterozygous SNPs, UGT1A1⁎6 (rs4148323) and UGT1A1⁎28 (rs8175347), and two adjacent heterozygous SNPs, K1637K (rs1117601...

Bilirubin, the product of heme catabolism, represents an important endobiotic of the endo-and xenobiotic metabolism system including drug-metabolizing enzymes, drug transporters, and drug-inducible ligandactivated transcription factors (LATFs). Bilirubin is of clinical concern since severe neonatal jaundice may lead to “kernicterus” and neurotoxicity (Kapitulnik, 2004). Hyperbilirubinemia in th...

The anticancer prodrug, irinotecan, is converted to its active form 7-ethyl-10-hydroxycamptothecin (SN-38) by carboxylesterases, and SN-38 is inactivated by UDP-glucuronosyltransferase (UGT)1A1-mediated glucuronidation. UGT1A9 also mediates this reaction. In a recent study, it was reported that the UGT1A9 IVS1+399 (I399)C>T polymorphism is associated with increased SN-38 glucuronidation both in...

Polymorphisms in UGT1A9 were associated with reduced toxicity and increased response to irinotecan in cancer patients. UDP-glucuronosyltransferase (UGT) protein expression, glucuronidation activities for 7-ethyl-10-hydroxycamptothecin (SN-38), and probe substrates of the UGT1A9 and UGT1A1 were measured in 48 human livers to clarify the role of UGT1A9 variants on the in vitro glucuronidation of ...

BACKGROUND Bilirubin is an antioxidant that suppresses lipid oxidation and retards atherosclerosis formation. An inverse association between serum bilirubin and coronary heart disease has been reported. Linkage studies have identified a major locus at the chromosome 2q telomere that affects bilirubin concentrations. A candidate gene in the linkage region encodes hepatic bilirubin uridine diphos...

A number of genetic risk factors have been implicated in the development of neonatal severe hyperbilirubinaemia. This includes mutations in the uridine glucoronosyl transferase 1A1 (UGT1A1) gene which is responsible for unconjugated hyperbilirubinemia in Gilbert's Syndrome. We studied the prevalence of UGT1A1 gene mutations in a group of Malay neonates to determine whether they are risk factors...

to determine the association between polymorphism of ugt1a1 gene and idiopathic hyperbilirubinemia in iranian neonates. fifty neonates with idiopathic hyperbilirubinemia and serum total bilirubin (stb) more that 15mg/dl and 50 neonates with idiopathic hyperbilirubinemia and serum total bilirubin (stb) less than 15mg/dl enrolled in this study. thymine-adenine (ta)  repeats in the promoter region...

BACKGROUND Gilbert syndrome is a clinically inconsequential entity of mild unconjugated hyperbilirubinemia caused by an A(TA)(n)TAA insertion polymorphism (UGT1A1*28) in the promoter region of the gene coding for the enzyme UDP-glucuronosyltransferase 1 (EC 2.4.1. 17; UGT1A1). Present methods for genotyping this polymorphism are laborious. METHODS Hybridization probes were designed complement...

N-Methyl-2-[3-((E)-2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]benzamide (axitinib) is an oral inhibitor of vascular endothelial growth factor receptors 1–3, which is approved for the treatment of advanced renal cell cancer. Human [C]-labeled clinical studies indicate axitinib’s primary route of clearance is metabolism. The aims of the in vitro experiments presented herein were to identify an...

We experienced a case of a 19-year-old man with Gilbert syndrome with concomitant hereditary spherocytosis. The patient presented with moderate unconjugated hyperbilirubinemia, and inherited etiology was strongly suspected. The diagnosis of Gilbert syndrome was confirmed by the genetic analysis of the UGT1A1 gene, demonstrating UGT1A1*28 and compound heterozygote UGT1A1*6. In addition, since th...