RESUMO
Alterations in the hepatic conjugation of bilirubin due to uridyl-diphosphate-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms have been proposed as risk factors to neonatal jaundice. Herein, we estimated the frequency of genotypes of the promoter region of UGT1A1 gene in newborns and evaluated its association with severe hyperbilirubinemia. Prospective study of cases and controls including all newborns admitted for phototherapy at HCPA, Brazil, during 9 months; 490 babies were enrolled and PCR was performed. Polymorphic genotypes were detected in 16% of the patients and 7 of the 10 possible genotypes were identified with higher prevalence of polymorphisms in Afro-descendants. In this sample, the variants of UGT1A1 were not associated to severe hyperbilirubinemia; other genic factors should be sought in this high miscegenation area of Brazil.
Assuntos
Glucuronosiltransferase/genética , Icterícia Neonatal/genética , Polimorfismo Genético , Sequência de Bases , Brasil/epidemiologia , Estudos de Casos e Controles , Frequência do Gene , Genótipo , Idade Gestacional , Humanos , Recém-Nascido , Icterícia Neonatal/enzimologia , Icterícia Neonatal/epidemiologia , Reação em Cadeia da Polimerase , Prevalência , Regiões Promotoras Genéticas , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Increased destruction of erythrocytes in patients with sickle cell disease results in chronic hyperbilirubinemia and leads to the formation of gallstones. OBJECTIVES: The objective of this study was to determine the combined influence of alpha thalassemia, fetal hemoglobin, and the UGT1A1 polymorphism on serum bilirubin levels and cholelithiasis in patients with sickle cell disease. METHODS: We analyzed 72 patients treated in the outpatient hematology unit of the Clinical Hospital of Porto Alegre. The alpha thalassemia trait was determined by multiplex polymerase chain reaction and the polymorphisms of UGT1A1 by capillary electrophoresis with tagged primers. RESULTS: Total and indirect bilirubin levels differed significantly between genotypes TA7/TA7 and TA6/TA6 (p < 0.05). Bilirubin levels were influenced by the UGT1A1 polymorphism but not by alpha thalassemia and fetal hemoglobin. There was no association between cholelithiasis and any of the variables studied. CONCLUSION: These preliminary findings suggest that the UGT1A1 gene can influence serum bilirubin levels in sickle cell anemia and serve as a tool to differentiate an acute hemolytic condition from a pre-existing condition of hyperbilirubinemia.
Assuntos
Anemia Falciforme/diagnóstico , Bilirrubina/sangue , Colelitíase/diagnóstico , Hemoglobina Fetal/genética , Glucuronosiltransferase/genética , Polimorfismo Genético , Talassemia alfa/diagnóstico , Adolescente , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/complicações , Anemia Falciforme/genética , Colelitíase/sangue , Colelitíase/complicações , Colelitíase/genética , Feminino , Hemoglobina Fetal/metabolismo , Expressão Gênica , Genótipo , Glucuronosiltransferase/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Talassemia alfa/sangue , Talassemia alfa/complicações , Talassemia alfa/genéticaRESUMO
The aim of the work was to determine the variation of UGT1A1 genotypes in patients with hemolytic anemia in the southern Brazil. Three hundred twenty-three patients with hemolytic anemia were genotyped for UGT1A1 along with 232 controls. Allelic and genotypic distribution did not differ among studied groups. The TA7/TA7 genotype presented a frequency that ranged from 3.2% to 18.0% (nonsignificant). Alleles TA5 and TA8 were also found in the sample, even though southern Brazil is a major Caucasoid region. Genotype prevalence was very similar to those of African origins, reflecting the diversity of ethnic origins and the high degree of admixture in southern Brazil. Further studies should be conducted to correlate the modulating role of UGT1A1 polymorphism with the clinical conditions of each patient with hemolytic anemia.