Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The reasons why heterozygotes for beta-thalassaemia have considerable variation in serum bilirubin levels are unknown. High levels of bilirubin could be related to the co-inherited Gilbert's syndrome, determined either by mutations of the coding region or by variation in the A(TA)nTAA motif of the promoter of the bilirubin UDP-glucuronosyltransferase gene (UGT-1). We sequenced the coding and the promoter region of UGT-1A or characterized the A(TA)nTAA motif of the promoter by denaturing gel electrophoresis of radioactive amplified products. The results were correlated with bilirubin levels in 49 beta-thalassaemia heterozygotes for codon 39 (CAG --> TAG) nonsense mutation. 21 normal individuals and 32 unrelated patients with Gilbert's syndrome served as controls. The coding sequence region of the UGT-1A was normal. Five beta-thalassaemia heterozygotes, who were homozygous for the extra (TA) bases in the A(TA)nTAA element of the promoter of UGT-1A, the configuration present in homozygosity in Gilbert's syndrome, had higher bilirubin levels compared to those with the (TA)6/(TA)7 or (TA)6/(TA)6 configurations. In the group of 32 patients with Gilbert's syndrome, 31 of whom had the (TA)7/(TA)7 configuration, we detected 14 heterozygotes for beta-thalassaemia, a figure much higher than predicted on the basis of the carrier rate. Homozygosity for the (TA)7 motif, the typical promoter configuration of Gilbert's syndrome, is one of the factors determining hyperbilirubinaemia in heterozygous beta-thalassaemia.
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PMID:Hyperbilirubinaemia in heterozygous beta-thalassaemia is related to co-inherited Gilbert's syndrome. 937 68

A 15-year-old boy was admitted to our hospital because of microcytic hypochromic erythrocytosis and hyperbilirubinemia in October 1996. The laboratory findings were RBC: 597 x 10(4)/microliter, Hb: 13.1 g/dl, Ht: 40.8%, MCV: 70fl, MCH: 22pg, total bilirubin: 3.2 mg/dl (indirect: 2.2 mg/dl), s-Fe: 99 micrograms/dl, and ferritin: 25 ng/ml. Routine liver function tests were normal. There were no findings of hemolysis except for an increase in serum indirect bilirubin and reticulocytes. Decreased erythrocyte osmotic fragility was observed. The patient's mother and sister also showed microcytic hypochromic erythrocytosis. PCR analysis of genomic DNA from this patient, his mother, and his sister confirmed the diagnosis of the alpha-thalassemia trait. However, the bilirubin-UDP-glucuronosyltransferase 1 (B-UGT 1) gene mutation and the findings of the fasting test indicated the simultaneous presence of Gilbert's syndrome. The association of these two diseases in the same patient appears to be rare, especially in Japan because of the low incidence of thalassemia in this country. We concluded that the hyperbilirubinemia was caused by decreased bilirubin clearance, not by increased erythrocyte destruction.
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PMID:[alpha-thalassemia accompanied with Gilbert's syndrome]. 979 7

The authors investigated whether the considerable variability in serum bilirubin levels (STB) found in transfusion-dependent beta-thalassemia, beta-thal intermedia, and heterozygous beta-thalassemia individuals could be related to the coexistence of Gilbert syndrome (GS). The promoter region [A(TA)nTAA] of the bilirubin UDP-glucuronosyltransferase gene (UGT1A1) was analyzed in a total of 128 beta-thalassemia individuals (108 transfusion-dependent beta-thal patients, 20 very mild beta-thal intermedia) and in 33 beta-thal heterozygotes. The control group consisted of 70 healthy children with no history of anemia. The frequency of GS genotype (TA)7/(TA)7 did not differ significantly between the groups studied. A significant difference was observed between serum bilirubin levels (STB) and GS genotypes (TA)7/(TA)7 and (TA)6/(TA)7 and also between (TA)7/(TA)7 and (TA)6/(TA)6 for all groups examined. These results confirm that the (TA)7/(TA)7 GS genotype is one of the factors accounting for the hyperbilirubinemia observed in beta-thalassemia major, intermedia, and heterozygous individuals.
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PMID:Gilbert syndrome associated with beta-thalassemia. 1176 96

Elevated erythrocyte destruction in sickle cell disease (SCD) results in chronic hyperbilirubinaemia and, in a subset of patients, cholelithiasis occurs. We investigated whether the (TA)n promoter polymorphism in the UDP-glucuronosyltransferase 1A1 gene (UGT1A1) may modify bilirubin metabolism, influencing bilirubinaemia, predisposition to cholelithiasis and subsequent cholecystectomy, in a group of 153 young SCD patients (mean age 12.0 +/- 9.0 years) predominantly of Bantu beta S haplotype. The concomitant effect of alpha thalassaemia was also analysed. Among the several UGT1A1 genotypes found, the most frequent were the (TA)6/(TA)6 (n = 37), (TA)6/(TA)7 (n = 60) and (TA)7/(TA)7 (n = 29). These groups of patients did not significantly differ in age, gender ratio and haemoglobin, foetal haemoglobin and reticulocyte levels. On the other hand, total bilirubin levels were significantly different between groups, with an increased (TA) repeat number being associated with higher bilirubinaemia. Furthermore, both cholelithiasis and cholecystectomy were more frequent in groups with higher (TA) repeat number, although the former association was not statistically significant. None of the mentioned parameters is statistically different within UGT1A1 groups with the presence of alpha thalassaemia. Thus, the UGT1A1 promoter polymorphism may represent an important nonglobin genetic modifier of Bantu SCD patients' clinical manifestations, even at a young age.
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PMID:Early modification of sickle cell disease clinical course by UDP-glucuronosyltransferase 1A1 gene promoter polymorphism. 1839 54