ABSTRACT Objectives This study aimed to evaluate the frequencies of the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) and methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphisms in obese patients with and without type 2 diabetes mellitus (T2DM). Subjects and methods These polymorphisms were analyzed by polymerase chain reaction in 125 patients with obesity, 47 (T2DM) and 78 (Control Group). Results No significant difference was found on comparing the T2DM and Control Groups in respect to the genotypic frequencies of the polymorphisms - (II: 13.3% vs. 12.0%; ID: 37.8% vs. 37.3; DD: 48.9% vs. 50.7%; CC: 36.2% vs. 39.0%; CT: 46.8% vs. 49.3%; TT: 17.0% vs. 11.7%), and alleles (I: 32.2% vs. 30.7%; D: 67.8% vs. 69.3%; C: 59.6% vs. 63.6%; T: 40.4% vs. 36.4%) and their synergisms in the pathophysiology of T2DM. On analyzing the T2DM Group, there were no significant differences in the presence of complications. In this population of Brazilian obese patients, no correlation was found between the ACE and MTHFR polymorphisms in the development of T2DM. Conclusion Analyzing only the group with diabetes, there was also no relationship between these polymorphisms and comorbidities.

The aim of this study was to determine the frequency of beta S-globin gene (βS globin) haplotypes and alpha thalassemia with 3.7 kb deletion (−α3.7kb thalassemia) in the northwest region of Paraná state, and to investigate the oxidative and clinical-hematological profile of βS globin carriers in this population. Of the 77 samples analyzed, 17 were Hb SS, 30 were Hb AS and 30 were Hb AA. The βSglobin haplotypes and −α3.7kb thalassemia were identified using polymerase chain reaction.Trolox equivalent antioxidant capacity (TEAC) and lipid peroxidation (LPO) were assessed spectophotometrically. Serum melatonin levels were determined using high-performance liquid chromatography coupled to coulometric electrochemical detection. The haplotype frequencies in the SS individuals were as follows: Bantu- 21 (62%), Benin - 11 (32%) and Atypical- 2 (6%). Bantu/Benin was the most frequent genotype. Of the 47 SS and AS individuals assessed, 17% (n = 8) had the −α3.7kb mutation. Clinical manifestations, as well as serum melatonin, TEAC and LPO levels did not differ between Bantu/Bantu and Bantu/Benin individuals (p > 0.05). Both genotypes were associated with high LPO and TEAC levels and decreased melatonin concentration. These data suggest that the level of oxidative stress in patients with Bantu/Bantu and Bantu/Benin genotypes may overload the antioxidant capacity.

This review discusses hemoglobin D-Punjab, also known as hemoglobin D-Los Angeles, one of the most common hemoglobin variants worldwide. It is derived from a point mutation in the beta-globin gene (HBB: c.364G>C; rs33946267) prevalent in the Punjab region, North-western Indian. Hemoglobin D-Punjab can be inherited in heterozygosis with hemoglobin A causing no clinical or hematological alterations, or in homozygosis, the rarest form of inheritance, a condition that is commonly not related to clinical symptomatology. Moreover, this variant can exist in association with other hemoglobinopathies, such as thalassemias; the most noticeable clinical alterations occur when hemoglobin D-Punjab is associated to hemoglobin S. The clinical manifestations of this association can be similar to homozygosis for hemoglobin S. Although hemoglobin D-Punjab is a common variant globally with clinical importance especially in cases of double heterozygosis, hemoglobin S/D-Punjab is still understudied. In Brazil, for example, hemoglobin D-Punjab is the third most common hemoglobin variant. Thus, this paper summarizes information about the origin, geographic distribution, characterization and occurrence of hemoglobin D-Punjab haplotypes to try to improve our knowledge of this variant. Moreover, a list of the main techniques used in its identification is provided emphasizing the importance of complementary molecular analysis for accurate diagnosis.

Background: Several studies have evaluated the oxidant and antioxidant status of thalassemia patients but most focused mainly on the severe and intermediate states of the disease. Moreover, the oxidative status has not been evaluated for the different beta-thalassemia mutations. Objective: To evaluate lipid peroxidation and Trolox equivalent antioxidant capacity in relation to serum iron and ferritin in beta thalassemia resulting from two different mutations (CD39 and IVS-I-110) compared to individuals without beta-thalassemia. Methods: One hundred and thirty subjects were studied, including 49 who were heterozygous for beta-thalassemia and 81 controls. Blood samples were subjected to screening tests for hemoglobin. Allele-specific polymerase chain reaction was used to confirm mutations for beta-thalassemia, an analysis of thiobarbituric acid reactive species was used to determine lipid peroxidation, and Trolox equivalent antioxidant capacity evaluations were performed. The heterozygous beta-thalassemia group was also evaluated for serum iron and ferritin status. Results: Thiobarbituric acid reactive species (486.24 ± 119.64 ng/mL) and Trolox equivalent antioxidant capacity values (2.23 ± 0.11 mM/L) were higher in beta-thalassemia heterozygotes compared to controls (260.86 ± 92.40 ng/mL and 2.12 ± 0.10 mM/L, respectively; p-value < 0.01). Increased thiobarbituric acid reactive species values were observed in subjects with the CD39 mutation compared with those with the IVS-I-110 mutation (529.94 ± 115.60 ng/mL and 453.39 ± 121.10 ng/mL, respectively; p-value = 0.04). However, average Trolox equivalent antioxidant capacity values were similar for both mutations (2.20 ± 0.08 mM/L and 2.23 ± 0.12 mM/L, respectively; p-value = 0.39). There was no influence of serum iron and ferritin levels on thiobarbituric acid reactive species and Trolox equivalent antioxidant capacity values. Conclusion: This study shows an increase of oxidative stress and antioxidant capacity in beta-thalassemia heterozygotes, mainly in carriers of the CD39 mutation.

OBJECTIVE: The oxidative stress in 20 sickle cell anemia patients taking hydroxyurea and 13 sickle cell anemia patients who did not take hydroxyurea was compared with a control group of 96 individuals without any hemoglobinopathy. METHODS: Oxidative stress was assessed by thiobarbituric acid reactive species production, the Trolox-equivalent antioxidant capacity and plasma glutathione levels. RESULTS: Thiobarbituric acid reactive species values were higher in patients without specific medication, followed by patients taking hydroxyurea and the Control Group (p < 0.0001). The antioxidant capacity was higher in patients taking hydroxyurea and lower in the Control Group (p = 0.0002 for Trolox-equivalent antioxidant capacity and p < 0.0292 for plasma glutathione). Thiobarbituric acid reactive species levels were correlated with higher hemoglobin S levels (r = 0.55; p = 0.0040) and lower hemoglobin F concentrations(r = -0.52; p = 0.0067). On the other hand, plasma glutathione levels were negatively correlated with hemoglobin S levels (r = -0.49; p = 0.0111) and positively associated with hemoglobin F values (r = 0.56; p = 0.0031). CONCLUSION: Sickle cell anemia patients have high oxidative stress and, conversely, increased antioxidant activity. The increase in hemoglobin F levels provided by hydroxyurea and its antioxidant action may explain the reduction in lipid peroxidation and increased antioxidant defenses in these individuals.

Human hemoglobin genes are located in α and β globin gene clusters in chromosomes 16 and 11, respectively. Different types of hemoglobin are synthesized according to the stage of development with fetal hemoglobin (α2γ2) (Hb F) being the main hemoglobin in the fetal period. After birth, there is a reduction (to about 1%) in Hb F levels and adult hemoglobin, Hb A (2α2β2), increases to more than 96% of total hemoglobin. However, some genetic conditions whether linked to the β-globin gene cluster or not are associated with high Hb F levels in adults. Among those linked to β-globin are hereditary persistence of fetal hemoglobin, delta-beta thalassemia (δβ-Thalassemia) and the XmnI polymorphism (-158 C > T). Other polymorphisms not related to β-globin gene cluster are known to influence the γ-globin gene expression in adulthood. The most relevant polymorphisms that increase concentrations of Hb F are the HMIP locus on chromosome 6, the BCL11A locus on chromosome 2, the Xp22.2 region of the X chromosome and the 8q region on chromosome 8. Findings from our research group studying genetic factors involved in γ-globin gene regulation in adults without anemia in the northwestern region of São Paulo State showed that high Hb F levels are influenced by the presence of hereditary persistence of fetal hemoglobin mutations and the XmnI polymorphism, suggesting that both genetic alterations characterize the molecular basis of the evaluated population.