Characterization Genotypic and Allelics of the Glutationa S-Transferase Class µ, Enzyme of the Metabolism of Xenobiotic
The gene of Glutathione S-transferase M1 located in the chromosome 1p13.3, code for cytosolic enzymes GST-mu. GSTs (EC 126.96.36.199) constitutes a family of multifunctional enzyme dimeric involved in the phase 2 of the metabolism of drugs and carcinogens, responsible for the biotransformation of xenobiotic and detoxification. The basic chemistry catalyzed by the GST involves glutathione GSH (?-glutamil-citeinil-glicine), that it carries through the linking of the tripeptide with toxic compounds, facilitating the conjugation of the electrophlic region of some hydrophobic substances, becoming more water-soluble and facilitating the elimination. Evidences exist of that homozigoto null (GSTM1 * O/O) has the increased relative risk in the development of malignant pathologies. The caucasian register bigger frequency of null allele. It has however a geographic and ethnic variation in relation to the presence or absence (null allele) of the alleles of GSTM1, that can influence the efficiency or interpretations of studies epidemiologists. This fact discloses the necessity of if knowing the allelics and genotypics frequencies of this enzymatic system, being these scarce data for the population of Porto Velho/RO, endemic region for malaria. To characterize these frequencies of system GSTM1, for the population of the city of Porto Velho is basic question in the interpretation of data in the interventions of control of endemic diseases. The samples had been genotyped way PCR following described protocl already for Fryer and cols (Biochem J. 295:313-315, 1993). standing out itself that the digestions with Hae II had been disclosed in PAGE 8%. 554 and 146 chromosomes of individuals of the villages of Candelária and Batestaca had been analyzed, ward of Porto Velho with riverine characteristics. The genotypics frequencies estimates for the null genotype had been 0,14 and 0,18 in Candelária and Batestaca, respectively. ?2 of the total distribution was 2.50, p = 0.1142, for Candelária, and ?2 = 13,63, p = 0,0002, for Batestaca. The significance observed in Batestaca can have to the small amostral size. In the association between phenotype of GSTM1 and infection for Plasmodium of malaria (asymptomatic, symptomatic and not infection), in the Candelária village, we observe that alelo *B presented greater frequency in all the fenótipos (symptomatic, asymptomatic infection and without infection), in the two more frequent infections of the region (facípara and vivax, 0.45-0.62, respectively). The genotype A/B was as the most frequent one, also in all the phenotype, being equal 0.27 and 0,15 (asymptomatic falciparum and vivax), 0.26 and 0.27 for symptomatic falciparum and vivax. The frequency of the null genotype was bigger (0,20) in symptomatic for malaria falcípara.
Advisor:Vera Engracia Gama de Oliveira
School:Fundação Universidade Federal de Rondônia
Source Type:Master's Thesis
Date of Publication:12/01/2005