Association of Serum Bilirubin and Functional Variants of Heme Oxygenase 1 and Bilirubin UDP-Glucuronosyl Transferase Genes in Czech Adult Patients with Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disorder worldwide. The aim of our study was to assess the role of bilirubin, and the heme oxygenase 1 (HMOX1) and bilirubin UDP-glucuronosyl transferase (UGT1A1) promoter gene variants, which are involved in bilirubin homeostasis, in the NAFLD development in adult patients. The study was performed on 84 patients with NAFLD and 103 age/sex-matched controls. Routine biochemistry, inflammatory markers, adipokines, and the fibrosis/steatohepatitis stage were determined in the NAFLD patients. The (GT)n/(TA)n dinucleotide variations in HMOX1/UGT1A1 gene promoters, respectively, were analyzed by fragment analysis. Compared to controls, serum bilirubin concentrations in NAFLD patients tended to be decreased, while the prevalence of phenotypic Gilbert syndrome was significantly low. Genetic variations in HMOX1 and UGT1A1 gene promoters did not differ between NAFLD patients and controls, and no relationship was found in the NAFLD patients between these gene variants and any of the laboratory or histological parameters. In conclusion, metabolism of bilirubin is dysregulated in NAFLD patients, most likely due to increased oxidative stress, since frequencies of the major functional variants in the HMOX1 or UGT1A1 gene promoters did not have any effect on development of NAFLD in adult patients.

Age and gender distribution among the patients with Gilbert’s syndrome

Aim. To analyze age and gender distribution in patients with Gilbert's syndrome.Materials and Methods. We consecutively recruited 115 patients with Gilbert's syndrome. All patients underwent genotyping of the rs8175347 polymorphism within the UGT1A1 gene using allele-specific polymerase chain reaction to confirm the diagnosis.Results. The age of initial diagnosis ranged from 3 years to 71 years, with the majority (44.3%) of cases detected ≤ 20 years of age. Mean ± standard error and median age of the diagnosis were 30.03 ± 1.72 years and 23 years. Despite the proportion of females and males among patients was similar, age distribution at primary diagnosis was significantly different across the genders. In women, Gilbert's syndrome was most frequently detected between 11 and 20 years (23.1%) and between 51 and 60 years (19.2%). In contrast, male adolescents were more prone to the development of Gilbert's syndrome, as 47.6% of male patients belonged to this age category.Conclusions. Variable age of Gilbert's syndrome diagnosis is probably determined by an individual combination of genetic causes (e.g., mutation of the UGT1A1 gene) and additional risk factors. Adolescents compose a significant proportion of patients. Because of relatively mild disease in many patients and unpredictability of the provoking factors, primary detection of Gilbert's syndrome can be delayed. Differences in age of Gilbert's syndrome diagnosis across the genders can be partially explained by organizational reasons associated with the current screening programs.

Identifying UGT1A1 gene mutations in Vietnamese patients with Gilbert syndrome

Gilbert’s syndrome (GS) is the most common inherited disorder of bilirubin metabolism, non-lethal, affecting 3-12% of the population. The genetic variants of the UDP- glucuronosyltransferase 1A1 (UGT1A1) gene might reduce the gene transcription activity and its enzyme expression, which affects the ability to conjugate glucuronidation in the liver. This study aimed to identify genetic variants of UGT1A1 in two Vietnamese sibling brothers with jaundice manifestations suspected GS. The peripheral blood samples of patients were used to extract genome DNA and sequence the enhancer, promoter, and coding all five exons of UGT1A1. Two pathogenic variants c.-3279T>G located in the phenobarbital responsive enhancer module (gtPBREM) and A(TA)7TAA of the TATA box in the promoter region were identified. They are twice common pathogenic variants that were reported in almost hyperbilirubinemia individuals from different populations. The obtained results improved the accuracy of medical diagnosis and warned the patients to be cautious in case they have to use medical drugs in the future.