Haptoglobin and myeloperoxidase (- G463A) gene polymorphisms in Brazilian sickle cell patients with and without secondary iron overload.

We aimed to investigate the influence of haptoglobin (Hp) and myeloperoxidase (MPO - G463A; dbSNP rs2333227) gene polymorphisms on 78 sickle cell patients of a public hospital in the Federal District/Brazil with and without iron overload, to evaluate a possible association between these polymorphisms and clinical variability, response to treatment and prognosis. Data were obtained through laboratory tests, questionnaires, research in medical records and analyses of polymorphisms using PCR-based methods. Positive correlations were found between Hp and ferritin levels, hydroxyurea treatment, hospitalisation for and sequelae from stroke; and between MPO and number of hospitalizations in the past 12 months and splenectomy. Significant associations of specific Hp genotypes with comorbidities were also found, while results suggested that MPO AA homozygosis could increase effects of asplenia. Deviation from Hardy-Weinberg equilibrium, compatible with heterozygous deficit, was observed for Hp polymorphism. Odds ratio suggested the possibility that increased chance of hospitalisation for stroke (OR = 6.346; IC 95% = 1.56-25.79; p = 0.005) and sequelae of stroke (OR = 6.556; IC 95% = 1.578-27.237; p = 0.005) could be associated with lower frequency of 1S-2 than expected. In the interaction analyses, significant effects between subjects were shown only in the group without overload for Hp polymorphism in hs-CRP levels (p = 0.000) and number of transfusions (p = 0.018), and for MPO polymorphism (p = 0.000) and the interaction Hp/MPO (p = 0.000) in hs-CRP values. Results corroborate others indicating biological differences between Hp*1 alleles and highlight the importance of this study in understanding the biological significance of Hp and MPO polymorphisms in clinical variability and response to treatment of sickle cell patients.

Superoxide dismutase, catalase, glutathione peroxidase and gluthatione S-transferases M1 and T1 gene polymorphisms in three Brazilian population groups

Antioxidants such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX1) reduce the oxidation rates in the organism. Gluthatione S-transferases (GSTs) play a vital role in phase 2 of biotransformation of many substances. Variation in the expression of these enzymes suggests individual differences for the degree of antioxidant protection and geographical differences in the distribution of these variants. We described the distribution frequency of CAT (21A/T), SOD2 (Ala9Val), GPX1 (Pro198Leu), GSTM1 and GSTT1 polymorphisms in three Brazilian population groups: Kayabi Amerindians (n = 60), Kalunga Afro-descendants (n = 72), and an urban mixed population from Federal District (n = 162). Frequencies of the variants observed in Kalunga (18 percent to 58 percent) and Federal District (33 percent to 63 percent) were similar to those observed in Euro and Afro-descendants, while in Kayabi (3 percent to 68 percent), depending on the marker, frequencies were similar to the ones found in different ethnic groups. Except for SOD2 in all population groups studied here, and for GPX1 in Kalunga, the genotypic distributions were in accordance with Hardy-Weinberg Equilibrium. These data can clarify the contribution of different ethnicities in the formation of mixed populations, such as that of Brazil. Moreover, outcomes will be valuable resources for future functional studies and for genetic studies in specific populations. If these studies are designed to comprehensively explore the role of these genetic polymorphisms in the etiology of human diseases they may help to prevent inconsistent genotype-phenotype associations in pharmacogenetic studies.

Evaluation of gene polymorphisms in exercise-induced oxidative stress and damage.

Many potentially significant genetic variants related to oxidative stress have been identified and performance in endurance sports is a multi-factorial phenotype. Thus, it was decided to investigate the influences of the haptoglobin (Hp), MnSOD (Val9Ala), CAT (21A/T), GPX1 (Pro198Leu), ACE, glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) genes' polymorphisms on the oxidative stress and damage suffered by human athletes (runners). Blood samples taken immediately after a race were submitted to genotyping, comet and TBARS assays, biochemical analyses of creatine kinase (CK), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). MnSOD significantly influenced results of CK and a possible association between Hp1F-1S and Hp1S-2 genotypes with a superior TBARS values was found. Higher or lower TBARS and CK values or DNA damage also depended on the interaction between Hp and ACE or GST genotypes, indicating that MnSOD and Hp polymorphisms can be determining factors in performance, at least for runners.

Glutathione S-transferase M1 and T1 polymorphisms in Brazilian African descendants.

The glutathione S-transferase gene family has an important role in the biotransformation and detoxification of different xenobiotics and endogenous compounds. Two polymorphic genes of this family, GSTM1 and GSTT1, present null alleles that consequently do not produce the respective enzyme when the genotype is homozygous. These polymorphisms are also interesting for population dynamics studies because they have great frequency variations among different ethnic groups and have been reported worldwide. The distribution of these alleles in urban and Amerindian populations in Brazil has been described, but none of those studies reported on African-descended rural populations. The aim of this study was to analyze the genotype frequency distribution of the GSTM1 and GSTT1 null alleles in an urban sample from the Federal District (n = 91) and in four semi-isolated African-descended populations: Mocambo (n = 55), Rio das Rãs (n = 117), Riacho de Sacutiaba (n = 34), and Kalunga (n = 68). The GSTM1 and GSTT1 null genotype frequencies in these populations range from 17% to 35% for GSTM1 and from 22% to 44% for GSTT1. These values are similar to those described in other African and African-descended populations. Despite this range, there is no distribution difference among the analyzed populations. Combined GSTM1 and GSTT1 null genotype frequencies range from 6% to 13% and are similar to European-derived populations, suggesting admixture with this ethnic group. This can be interpreted as a European contribution to these African-descended populations. Regarding the urban population in the Federal District, our results suggest an important African and European contribution.

Distribution of glutathione S-transferase GSTM1 and GSTT1 null phenotypes in Brazilian Amerindians

The distribution of glutathione S-transferase (GST) GSTM1 and GSTT1 null phenotype frequencies in two Brazilian Amerindian tribes, the Munduruku tribe from Missão Cururu village (79 individuals) and the Kayabi tribe (41 individuals), was analyzed by polymerase chain reaction (PCR) amplification. The GST null phenotype frequencies for the Munduruku sample were 0 percent for GSTM1 and 27 percent for GSTT1 while for the Kayabi sample the null phenotype frequencies were 27 percent for GSTM1 and 29 percent for GSTT1. This is the first report of the absence of the GSTM1 null phenotype in any ethnic group.