ORIGINAL ARTICLESGenetic factors related to unconjugated hyperbilirubinemia amongst adultsHuang, Ching-Shana b; Huang, May-Jenb; Lin, Min-Shungc; Yang, Sien-Singd; Teng, Hsiu-Chene; Tang, Kung-ShengaAuthor Information Departments of aMedical Technology eMedical Management, Fooyin University, Kaohsiung Departments of bLaboratory Medicine cFamily Medicine dLiver Unit, Cathay General Hospital, Taipei, Taiwan Sponsorship: This study was supported by a grant from the National Science Council, Taiwan; contract number: NSC 92-3112-B-242-001. Correspondence and requests for reprints to Professor Ching-Shan Huang, Department of Laboratory Medicine, Cathay General Hospital, no. 280, Sec. 4, Jen Ai Road, Taipei 106, Taiwan Tel: +886 2 2636 0450; fax: +886 2 26360462; e-mail: [email protected] Received 6 September 2004 Accepted 26 October 2004 Pharmacogenetics and Genomics: January 2005 - Volume 15 - Issue 1 - p 43-50 Buy Abstract Some variations in the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene are involved in the development of unconjugated hyperbilirubinemia. We hypothesize that other genetic factors may also be associated with this disease. A total of 227 adults with normal routine haematology and liver function (apart from bilirubin testing for which they revealed bilirubin ≥25.7 μmol/l and unconjugated bilirubin/total bilirubin ≥80%), and 235 sex- and age-matched controls, were recruited. All subjects were analysed for UGT1A1, glucose-6-phosphate dehydrogenase (G6PD) and organic anion transporter polypeptide 2 (OATP2) genotypes using polymerase chain reaction-restriction fragment length polymorphism. The results indicated that G6PD deficiency, variant UGT1A1 gene and variant OATP2 gene were risk factors for hyperbilirubinemia. The odds ratios (OR) (with 95% confidence interval) were 220.83 (34.68–1406.30), 73.61 (17.01–318.63), 45.15 (11.19–182.22), 15.46 (4.35–54.99) and 6.51 (1.83–23.09), respectively, for individuals featuring the common UGT1A1/OATP2 haplotypes homozygous/heterozygous, compound heterozygous/heterozygous, compound heterozygous/wild-type, heterozygous/heterozygous and heterozygous/wild-type variations amongst subjects with normal G6PD activity. Amongst the subjects with G6PD deficiency, the OR was 159.00 (24.57–1028.94) for individuals carrying variations in both UGT1A1 and OATP2 genes. The UGT1A1/OATP2 haplotypes homozygous/wild-type, homozygous/compound heterozygous and homozygous/homozygous for G6PD normal and variant/wild-type for G6PD deficient individuals were only observed in the case group, and not in the control group. Amongst hyperbilirubinemic adults, bilirubin values tended to parallel variation status of their haplotypes. Adults featuring certain haplotypes in UGT1A1, OATP2 and G6PD genes face a high risk of developing unconjugated hyperbilirubinemia. © 2005 Lippincott Williams & Wilkins, Inc.