Viorica E. Radoi1,2, Radu I. Ursu1,2, Elena Poenaru3, Cosmin Arsene1, Camil L. Bohiltea2, Roxana Bohiltea4
1) Synevo Romania, Central Laboratory, Medical Genetics Department; and
2) Department of Medical Genetics; 3) Department of Medical Informatics, Biostatistics, Marketing and Medical Technology; 4) SUUB Obstetrics-Gynecology Department,Carol Davila University of Medicine and Pharmacy, Faculty of General Medicine Bucharest, Romania
ABSTRACT Background & Aims: Gilbert syndrome (GS) is characterized by unconjugated hyperbilirubinemia without liver disease or overt hemolysis and it is found in 3-10% of the general population. Inherited hyperbilirubinaemia is attributable to a reduced UGT1A1 activity. The UGT1A1 promoter (TA) repeats variants are documented of being involved in abnormally elevated bilirubin levels. The aim of the present study is to analyze the impact of UGT1A1 promoter variants on bilirubin levels in Romanian patients clinically supected with GS. Methods: The study group included 897 subjects: 292 GS patients and 605 healthy controls. Genomic DNA was extracted from the peripheral blood leukocytes. All individuals were screened for the presence of the (TA) insertion in the TATA box region of UGT1A1 gene by PCR amplification. This case-control study was conducted at the Department of Medical Genetics, Synevo, Romania.
Results: UGT1A1*28 (7TA) revealed the highest frequency (61.87%) of all individuals, while the UGT1A1*1 (6TA) allele was found in 36.79%. We identified two other variants of the UGT1A1 gene, depending on the number of TA repeats in the promoter: 5TA (0.61%) and 8TA (0.72%). The (TA)7/7 homozygous genotype was identified in 32.33% of all individuals, while the (TA)6/7 heterozygous genotype was the most prevalent (57.64%). The wild type (TA)6/6 was identified in 7.36% of the whole cohort. Conclusions: Because other polymorphisms have been associated with GS, the absence of the UGT1A1*28 allele does not rule out this condition. The results suggest that in the Romanian population there is a strong correlation between the UGT1A1*28 polymorphism and hyperbilirubinemia in patients with GS. Key words: Gilbert syndrome – UGT1A1 gene – variant – hyperbilirubinemia – promoter – (TA) repeats Abbreviations: DNA: deoxyribonucleic acid; EDTA: ethylene diamine tetraacetic acid; GS: Gilbert syndrome; OMIM: Online Mendelian Inheritance in Men; PCR: polymerase chain reaction; TA: thymine-adenine; UDP: uridine diphosphate; UGT: uridine diphosphate glucuronosyltransferase; UGT1A1: UGT 1A isoform 1.