Population analysis of xenobiotic metabolizing genes in South Brazilian Euro and Afro-descendants

Abstract

Individual variability in xenobiotic metabolism has been associated with susceptibility to developing complex diseases. Genes involved in xenobiotic metabolism have been evaluated in association studies; the difficulty of obtaining accurate gene frequencies in mixed populations makes interpretation of the results difficult. We sought to estimate population parameters for the cytochrome P450 and glutathione S-transferase gene families, thus contributing to studies using these genes as markers. We describe the frequencies of six genes (CYP1A1, CYP2D6, CYP2E1, GSTM1, GSTT1, and GSTP1) and estimate population parameters in 115 Euro-descendants and 196 Afro-descendants from Curitiba, South of Brazil. PCR-based methods were used for genotyping, and statistical analysis were performed by AMOVA with ARLEQUIN software. The mutant allele frequencies in the Afro-descendants and Euro-descendants, respectively, were: CYP1A1*2A = 30.1% and 15.2%; CYP2D6*4 = 14.5% and 21.5%; CYP2E1*5B = 7.9% and 5%; GSTP1*B = 37.8% and 28.3%. The null genotype frequencies were: GSTM1*0 = 36.8% and 46.1%; GSTT1*0 = 24.2% and 17.4%.Key words: CYP, GST, population study. Genetic marker studies assessing individual backgrounds from specific populations can provide information on gene flow, evolutionary history, and population dispersions, and can also help in the prediction of risks for particular diseases. Based on these studies, pharmacogenetic data have shown significant inter-and intra-population differences in the metabolism, efficiencies, and toxicities of several types of drugs. These findings have important implications for the management and treatment of human diseases (Kittles and Weiss, 2003).Many different enzyme families are involved in xenobiotic metabolism, including cytochrome P450 (CYPs) in phase I, as well as glutathione S-transferases (GSTs) and N-acetyl-transferases (NATs) in phase II (Autrup, 2000). Several genes of the CYP family have been studied in many populations (e.g., Europeans, Africans, Asians, and their mixed descendants) in case-control studies of complex diseases. With regard to cancers, these studies focus primarily on lung, breast, and head and neck tumors (Olshan et al.,

Metabolic Polymorphisms and Clinical Findings Related to Benzene Poisoning Detected in Exposed Brazilian Gas-Station Workers

“…The MPO variant allele showed no difference. Except for GSTM1 and CYP2E1 1053C > T, the allele frequencies were similar to the findings of most other studies [ 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ]. Chen et al .…”

Lack of association of CYP1A1-MspI SNP and GSTM1 null genotypes with cancer in a Brazilian family with unusually high cancer incidence

“…Frequencies of 38.03% for the null genotype (-/-) and 61.97% for the positive genotype [heterozygous (+/-) and positive homozygous (+/+)] for the GSTM1 gene were observed (Table 1). These values are also close to that expected in samples of Brazilian populations (Miller et al, 1997;Arruda et al, 1998;Hatagima et al, 2000;Rossini et al, 2002;Maciel et al, 2009). Members of this homozygous sample CYP1A1-MspI (m1/m1) who were also homozygous GSTM1 null genotype (-/-) were not found.…”

Environmental exposure to benzene: evaluation of urinary S-PMA and polymorphism (CYP2E1-1293G>C and NQO1 609C>T) in Campos Elíseos residents, Duque de Caxias, Rio de Janeiro State, Brazil

“…The genotype and allele frequencies of the study population are presented in Table 4. The allele and genotype distribution obtained in this study is similar to that reported in other studies evaluating the same polymorphisms in populations subjected to varying occupational and environmental exposure benzene concentrations 26,34,38,47,48,49,50,51,52,53,54 . The genotype distribution displayed a Hardy-Weinberg shift for the NQO1 and CYP2E1 genes.…”