Duplicação [TA] na região promotora do gene UGT1A1

: revisão sistemática e meta-análise

Abstract

The Gilbert Syndrome (GS) is a common clinical entity characterized by a benign form of unconjugated hyperbilirrubinemia in the absence of liver dysfunction and hemolysis. The diagnosis, initially presumptive in nature, began to use molecular characterization when, in 1995, were described the first mutations in UDP – glucuronosyltransferase-1 (UGT1A1). In particular, a duplication of two nucleotides [TA] in the promoter region of the gene, which has revealed itself as the leading cause of the GS in the Caucasian population studied. Affected individuals are homozygous for the variant of the promoter and they have seven despite of six repeats. Since then, many studies have been undertaken in order to relate this mutation with other pathologies, as well as some therapies used as chemotherapeutic agents or estrogen therapy. The aim of this study was to compile and synthesize the literature to calculate the global frequency, and frequency by country and continent, of TA duplication in the promoter region of the gene, associated with GS. One hundred studies were included in this study, conducted in twenty-nine countries of four continents. No studies were obtained from Africa. Is was obtained an overall frequency of 4,8% for genotype 7/7 and of 21,8% for allele 7. The frequencies obtained per continent were, 10,5% in Europe, 10,7% in North America, 10,2% in South America, 13,8% in Central America, 15% in Oceania and 1% in Asia. Statistical analysis of Cochran Q and I2 allowed us to evaluate the homogeneity of the studies included, concluding heterogeneity (p<0,001, I2= 92,3% (genótipo 7/7); (p<0,001, I2= 96% (alelo 7)), at global. In conclusion, thus study demonstrated that there is heterogeneity among the various studies included. With the exception of Asia, all countries have a high prevalence of this mutation, which justifies its systematic research, both in diagnosis, as in its association with other diseases that also causes hyperbilirrubineamia, and in situations where the deficit of UGT1A1 enzyme is associated with decreased hepatic metabolism of some drugs.

Date of Award	Feb 2012
Original language	Portuguese
Awarding Institution	Universidade Católica Portuguesa
Supervisor	Elísio Costa (Supervisor) & Rui Pimenta (Co-Supervisor)