Frequency of UGT1A1*28 (Gibert´s syndrome) in patients with chronic hepatitis C virus and healthy donors / Freqüência do alelo UGT1A1*28 (síndrome de Gilbert) em pacientes portadores de hepatite crônica C e em controles sadios
AUTOR(ES)
Marcelo Moreira Tavares de Souza
DATA DE PUBLICAÇÃO
2009
RESUMO
Gilberts syndrome is a benign condition characterized by unconjugated hiperbilurubinemia that occurs in the absence of hemolysis or liver chronic disease. It is clinically manifested by intermittently jaundice, triggered by exposition to physical stress, low calory diet, among others. The genetic base is the reduction of the activity of UDP-glucuronosyltransferase enzyme described in 1995: in a Caucasian population, all patients studied presented a Thymine Adenine (TA) addition in the TATA box region in both alleles of the UGT1A1 gene promoter. Although, Gilberts syndrome has been considered a benign condition, recently it has been associated to hiperbilirrubinemia and other adverse events during the utilization of some drugs such as Indinavir and Irinotecan. Another important issue to consider is that bilirubin is used to evaluate the severity of liver dysfunction in chronic liver diseases. The presence of this mutation in those patients could increase bilirubin levels, overestimating liver damage. The aim of this study were: 1) to verify the frequency of the genotype UGT1A1*28 (TA7/7) in blood donors and in chronic hepatitis C patients from the Gastroenterology outpatients clinics of the University of São Paulo School of Medicine; 2) to establish a relationship with TA7/7 genotype and bilirubin elevation in chronic hepatitis C patients and 3) to evaluate the fragment analysis technique to screening and genotyping the Gilbert syndrome. The frequencies of TA7/7 genotype found in blood donors group were 9.6% (30/313) and in the chronic hepatitis C group were 10% (51/494). The TA7/7 genotype seems to be related with increase of bilirubin. The fragment analysis technique is fast and able to a large scale screening approach. The genetic background of Brazilian population is highly heterogeneous. It is comprised of Caucasians, Africans, Indians, Orientals and others. The data suggests that genetic variation of promoter region of UGT1A1 gene is high among patients with bilirubin levels greater than 1 mg/dl, and UGT1A1*28 genotypes should be considered when evaluating chronic hepatitis C patients with hiperbilirubinemia.
ASSUNTO(S)
polymorphism hepatite c jaundice gilbert syndrome hiperbilirubinemia bilirubin hepatitis c virus bilirrubina hiperbilirrubinemia icterícia doença de gilbert polimorfismo genético
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