Ancestralidade e frequência de genótipos nulos dos genes GSTM1 e GSTT1 em uma população de longevos do Nordeste Brasileiro

Abstract

INTRODUCTION:the Glutathione S-transferases (GSTs) are an important superfamily of phase II metabolic antioxidant isoenzymes involved in the xenobiotic biotransformation process. The GSTM1 (Glutathione S-Transferase Mu 1) and GSTT1 (Glutathione S Transferase Theta-1) genes have a preponderant role for the detoxification of the body. However, the presence of allelic deletion polymorphism in homozygosis (GSTM1*0 GSTT1*0) of both genes lead to total loss of the enzymatic function. The frequence of the null GSTM1*0 GSTT1*0 allele is very variable in different populations, being associated with an increased risk of cancer and other diseases. There are many studies on the frequency of null alleles in different human populations of the world, but few studies that have associated ancestry, applying molecular markers, with these frequencies.OBJECTIVE: This study aimed to analyze the frequency of null alleles of GSTM1 and GSTT1 and their corresponding Amerindian, African and European ancestry, in a population of long-lived elders in the Northeast hinterlands of Brazil.MATERIAL AND METHOD: The sample was composed by 72 long-lived elders, of age between 80 and 102, living in the municipality of Brejo dos Santos-Paraíba. To determine the ancestry, it was used 10 and 41 Single-Nucleotide Polymorphisms (SNPs) associated with the genes GSTM1 and GSTT1 of the Affymetrix array, and the data analysis was done by the Genotyping console software. The determination of null genotypes frequency was done by multiplex Polymerase Chain Reaction (PCR) and gel electrophoresis. RESULTS: The observed frequency was 36.1% and 8.3% for null alleles of GSTM1 and GSTT1 respectively. For ancestry of null genotypes of GSTM1, 13.4% were Africans, 82.7% European, and 3.9% of Native American ancestry. For the null genotypes of GSTT1, 8.3% were Africans, 66.7% European, and 25.0% Native American. The distribution frequency of GSTM1 and GSTT1 alleles was not significantly different between the African, European and Amerindian haplotypes, with p=0,389 and p=0,102. The fact that the frequency of the GSTM1 null allele was higher than of the GSTT1 gene was in agreement with the published literature. Besides, similar with previous studies carried out with different human populations, the null alleles of both genes were more frequently associated with the European ancestry and less with the African ancestry.CONCLUSIONS: In view of the evidence found, we suggest that the studied population can serve as a model in case-control studies with the aim of investigating associations between the null alleles of GSTM1 and GSTT1 with different types of cancer. As the study population was very homogeneous, this approach can overcome the problem that different populations accumulate different risk factors that can obscure genetic differences.