Role of co-inherited Gilbert syndrome on hyperbilirubinemia in Indian beta thalassemia patients

Autor:	Kanjaksha Ghosh, Pooja Dabke, Anita Nadkarni, Roshan B. Colah
Rok vydání:	2014
Předmět:	Gilbert Syndrome congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Genotype Bilirubin India chemistry.chemical_compound Gene Frequency hemic and lymphatic diseases Internal medicine medicine Coding region Humans Glucuronosyltransferase Nucleotide Motifs Dinucleotide Repeats Promoter Regions Genetic Unconjugated hyperbilirubinemia Hyperbilirubinemia Genetics business.industry beta-Thalassemia nutritional and metabolic diseases Beta thalassemia Promoter Hematology medicine.disease Endocrinology chemistry Mutation Bilirubin levels BETA-THALASSEMIA INTERMEDIA Gilbert Disease business
Zdroj:	Hematology (Amsterdam, Netherlands). 19(7)
ISSN:	1607-8454
Popis:	Gilbert syndrome is characterized by mild unconjugated hyperbilirubinemia. The high levels of bilirubin could be related to the co-inheritance of Gilbert syndrome determined either by mutations of the coding region or by variation in the (TA)n motifs of the promoter region of the bilirubin UGT1A1 gene. The co-inheritance of Gilbert syndrome has been reported to elevate bilirubin levels in beta thalassemia and sickle cell disease patients. Aim In this study, we have tried to investigate whether the variability in serum bilirubin levels found in transfusion-dependent beta thalassemia, beta thalassemia intermedia, and heterozygous beta thalassemia individuals could be related to the coexistence of Gilbert syndrome.The promoter region (TA)n motifs of the bilirubin UGT1A1 gene were analyzed in 104 beta thalassemia individuals. The control group consisted of 50 healthy individuals.The analysis of the UGT1A1 promoter showed three (TA) motifs: (TA)5, (TA)6, and (TA)7. The frequency of genotype (TA)7/(TA)7 did not differ significantly between the groups studied. A significant difference was observed in mean serum bilirubin levels between individuals showing (TA)7/(TA)7 and (TA)6/(TA)6 genotypes and also between (TA)7/(TA)7 and (TA)6/(TA)7 genotypes among all groups studied. According to the beta genotype, no differences were observed between mean serum bilirubin levels in the three groups (β(+)/β(+), β(0)/β(+), and β(0)/β(0)).These results indicate that the (TA)7/(TA)7 configuration is one of the factors responsible for hyperbilirubinemia and, therefore, seems to interfere with the clinical expression of homozygous beta thalassemia. This emphasizes the role played by co-inherited modifying genes on clinical heterogeneity of monogenic disorders.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eb2a1a6c26533cad3f3a1d8c3d0e3940 https://pubmed.ncbi.nlm.nih.gov/24620945 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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