Caracterização molecular da desidrogenase da glicose 6-fosfato e hemoglobinopatias em pacientes com malária por plasmodium vivax

Abstract

Background: The understanding of malaria disease has greatly improved in the last few years. Despite decades of research against the disease, it continues to be a major public health problem. The genetic component of malaria susceptibility is complex and evaluating these determinants of susceptibility and deciphering the mechanisms involved may lead to the discovery of new vaccines or targets for pharmacological agents. Main. Molecular characterization of glucose-6-phosphate dehydrogenase (G6PD) and hemoglobin profile in patients with vivax malaria from Manaus-AM. Methods. For molecular characterization of G6PD were performed RFLP-PCR technique and qRT-PCR in 162 patients. Hemoglobin profile was determined by Highperformance liquid chromatography in 178 patients. Results. The hemoglobin profle showed 106 AA (92.7%), 09 AS (5.05%) e 04 AC (2.25%). These results demonstrated a lower frequency of severe malaria in AC (25%). Our results demonstrated the presence of nine (09) AS and four (04) AC, totaling 7.30% of the patients. Our results showed a lower frequency of severe malaria in AC group. This correlation among hemoglobin genotypes showed significant correlation between AA and AC (Neutrophils (p = 0.019), Band neutrophils (p = 0.049), Eosinophils (p = 0.046), Mean Cell Volume (p=0.004), Mean Cell Hemoglobin (p =0.008), there was no correlation between AA and the AS. The RDW was our only correlation between AA v/s AS (p=0.039) and AA v/s AC (p=0.019). The parasitaemia fever was the most frequent event in our study patients, occurring at 92.30% (12/13) of patients with AS/AC. The parasite density was lower in patients with AS (9352.35 ± 11622.78) and AC (11604.80 ± 11931.85) when compared with AA genotype (32431.57 ± 88719.63), but without statistical significance (p = 0.854). Of male presented 15.85% (13/82) for A− and 6.10% (05/82) Chatham variants, while 11.25% (09/80) of female presented A− in heterozygous and 1.25% (1/80) in homozygous. Male with G6PD A− demonstrated a higher frequency of severe malaria (OR=2.01, p=0.020) and strongly associated with previous malaria episodes (OR=2.35, p=0.004). When compared with G6PD wild type, male patients A− presented high platelet (p=0.009), lactate dehydrogenase (p<0.001) and direct bilirubin (p=0.045), while decreased in Gamma-Glutamyl transpeptidase (p=0.035). Both gender presented decreased of erythrocytes (p=0.002) (p=0.015), hemoglobin (p=0.017) (p=0.031) and hematocrit (p=0.013) (p=0.020), male and female, respectively. We observed decreased hemoglobin (p=0.018), hematocrit (p=0.014), platelets (p=0.003), reticulocyte count (p<0.001) and glucose level (p=0.031) among male patients in severe malaria with G6PD A− compared to severe malaria patients with wild type allele. Conclusion. These results reveal important roles for malaria s hemoglobin genotypes clinical patients outcomes, and studies are warranted to determine their involvement in severe malaria as well as it possible mechanism of action. In summary, few G6PD mutations studies were performed from Amazonian communities. Additional G6PD deficiency surveys in both these areas of high P. vivax endemicity would be valuable, particularly focused in areas of high population density.