CYP1A1, GSTM1, GSTT1 and GSTP1 polymorphisms in an Afro-Brazilian group

Gene polymorphisms involved in the metabolism of drugs and chemical carcinogens seem to be responsible for differences in the susceptibility of individuals to cancer, but genetic population studies are needed to characterize these polymorphisms in different ethnic populations. We investigated polymorphisms of the cytochrome P450 (CYP) gene CYP1A1 and the glutathione S-transferase (GSTs) genes GSTM1, GSTT1 and GSTP1 in a sample of Afro-Brazilians from the southern Brazilian city of Porto Alegre to verify if there were ethnic differences compared to the polymorphisms of the same genes in a previously described sample of Brazilians of European descent from the same city. The allele frequencies detected in the Afro-Brazilian population investigated in this study were CYP1A1*2A (30 percent) and GSTP1*Val (42 percent) while the frequency of the GSTM1 null genotype was 34 percent and that of the GSTT1 null genotype was 28 percent. Significant differences in genotype distribution and allelic frequencies were detected between Brazilians of African and of European descent from Porto Alegre in terms of the polymorphisms CYP1A1*2A (p = 0.003), GSTP1-Ile105Val (p = 0.002) and the GSTM1 null genotype (p = 0.01) but there was no detectable significant difference in respect to GSTT1 null genotype frequencies.

CYP1A1, CYP2E1, GSTM1, GSTT1, GSTP1, and TP53 polymorphisms: do they indicate susceptibility to chronic obstructive pulmonary disease and non-small-cell lung cancer?

Gene polymorphisms of phase I (CYP1A1 and CYP2E of cytochrome P,) and phase II (GSTM1, GSTT1 and GSTP1 of glutathione-S-transferase,) enzymes and the TP53 tumor suppressor gene were studied as markers in a sample of 262 Brazilians of European descent, the sample consisting of 97 patients with non-small-cell lung cancer (NSCLC), 75 patients with chronic obstructive pulmonary disease (COPD) and 90 control individuals. For NSCLC, we found no significant relationship between any of the markers studied and susceptibility to this disease. With respect to COPD, although the distribution of the CYP1A1, GSTM1, GSTP1, GSTT1 and TP53 genotypes was similar to that of the controls the frequency of the CYP2E1*1A/*5B heterozygote was about 6 times higher in COPD patients than in controls (OR= 6.3; CI = 1.1-35.5 for p = 0.04). Individuals who presented the GSTT1 null phenotype and GSTP1 Ile/Val genotype had a risk about four times higher (OR= 4.0; CI = 1.2-14.6 for p = 0.02) of having COPD than individuals without these genotypes, the same being true for individuals having the GSTT1 null phenotype and CYP1A1*1A/*2A genotype (OR= 3.7; 1.1-14.6 for p = 0.04).These results suggest that the CYP2E1 and GSTT1 + GSTP or GSTT1 + CYP1A1 polymorphisms may be predictive of susceptibility to COPD, at least in this population of European ancestry.

(TTTA)n polymorphism of CYP19 (aromatase gene) in Euro- and Afro-Brazilians

We investigated the polymorphic tetranucleotide repeat (TTTA)n located in the fourth intron of the CYP19 gene in two Brazilian populations. The frequencies of the five common alleles (A) in Euro- and Afro-Brazilians were, respectively: seven repeats (A5), 0.586 and 0.80; eight repeats (A4), 0.092 and 0.06; nine repeats (A3), 0.014 and 0.01; eleven repeats (A2), 0.284 and 0.09; twelve repeats (A1), 0.021 and 0.04. In addition, one Euro-Brazilian individual had a rare allele with 13 repeats. The allelic frequencies in Euro- and Afro-Brazilians differed statistically (p < 10-3). The two samples were found to be in Hardy-Weinberg equilibrium (p = 0,828 and p = 0,995).

Phosphoglucomutase proteins in human milk

O polimorfismo do loco 4 da fosfoglicomutase foi investigado em uma amostra de colostro obtida de 652 mulheres (60% brancas e 40% negras), coletada 24 a 48 hs. após o parto, em Porto Alegre, Brasil. Uma nova amostra de leite foi obtida de 175 dessas mulheres com cerca de 17 dias de lactaçäo. No colostro observou-se um acentuado desvio no equilíbrio de hardy-Weinberg, havendo em geral um excesso de homozigotos e deficiência de heterozigotos. No leite, no entanto, esse desequilíbrio näo ocorreu. As diferenças entre as duas distribuiçöes säo devidas à detecçäo de padröes nas amostras que näo apresentavam atividade no primeiro período, assim como a variabilidade na ativaçäo enzimática, que pode ocorrer no início da lactaçäo. As frequências gênicas no leite (n = 175) foram: brancos (n = 127) PGM4*1 = 0,20, PGM4*2 = 0,41, PGM4*3 = 0,38, PGM4*4 = 0,01; negróides (n = 48) PGM4*1 = 0,15, PGM4*2 = 0,52, PGM4*3 = 0,32 e PGM4*4 = 0,01

Effects of integerrimine on the implantation and intrauterine development of mice

Fêmeas gestantes de camundongos foram tratadas com o alcalóide pirrolizidínico integerrimina e foram analisadas quanto à perda pré e pós-implantaçäo e induçäo de malformaçöes congênitas. As fêmeas foram tratadas nos estágios de 0-10 horas, 58-64 horas, 5§ e 8§ dias gestacionais, com as doses de 0;25;37,5 e 50 mg/kg de peso corpóreo. Os resultados mostram que 1) o estágio 0-10 horas é o mais sensível para perdas pré-implantaçäo na linhagem C57BL/6; 2) os estágios de 3§ e 8§. dias säo mais sensíveis para perdas pós-implantaçäo para C57BL/6; 3) a integerrimina induz malformaçöes em fetos da linhagem C57BL/6 cujas mäes foram tratadas no 3§ dia gestacional. A linhagem C3H/HeJ näo apresentou malformaçöes embrionárias nos estágios e doses analisadas