RESUMO
The invasion of human erythrocytes by Plasmodium falciparum merozoites requires interaction between parasite ligands and host receptors. Interaction of PfRh5-CyRPA-Ripr protein complex with basigin, an erythrocyte surface receptor, via PfRh5 is essential for erythrocyte invasion. Antibodies raised against each antigen component of the complex have demonstrated erythrocyte invasion inhibition, making these proteins potential blood-stage vaccine candidates. Genetic polymorphisms present a significant challenge in developing efficacious vaccines, leading to variant-specific immune responses. This study investigated the genetic variations of the PfRh5 complex proteins in P. falciparum isolates from Lake Victoria islands, Western Kenya. Here, twenty-nine microscopically confirmed P. falciparum field samples collected from islands in Lake Victoria between July 2014 and July 2016 were genotyped by whole genome sequencing, and results compared to sequences mined from the GenBank database, from a study conducted in Kilifi, as well as other sequences from the MalariaGEN repository. We analyzed the frequency of polymorphisms in the PfRh5 protein complex proteins, PfRh5, PfCyRPA, PfRipr, and PfP113, and their location mapped on the 3D protein complex structure. We identified a total of 58 variants in the PfRh5 protein complex. PfRh5 protein was the most polymorphic with 30 SNPs, while PfCyRPA was relatively conserved with 3 SNPs. The minor allele frequency of the SNPs ranged between 1.9% and 21.2%. Ten high-frequency alleles (>5%) were observed in PfRh5 at codons 147, 148, 277, 410, and 429 and in PfRipr at codons 190, 255, 259, and 1003. A SNP was located in protein-protein interaction region C203Y and F292V of PfRh5 and PfCyRPA, respectively. Put together, this study revealed low polymorphisms in the PfRh5 invasion complex in the Lake Victoria parasite population. However, the two mutations identified on the protein interaction regions prompts for investigation on their impacts on parasite invasion process to support the consideration of PfRh5 components as potential malaria vaccine candidates.
RESUMO
BACKGROUND: One of the most important organ involvements in psoriasis is atherosclerotic cardiovascular disease. Homocysteine is known to have atherogenic properties, but some inconsistency exists in the literature about its probable role as a risk factor of cardiovascular disorder in patients with psoriasis. OBJECTIVE: Because of some controversies, we compared homocysteine levels and related parameters of metabolic cycles in patients with psoriasis and healthy individuals. METHODS: This case-control study was conducted on 50 patients with psoriasis and 50 healthy individuals as the controls. Serum homocysteine, vitamin B12 levels, and erythrocyte folate concentrations were checked in all participants. RESULTS: Mean serum homocysteine, erythrocyte folate, and vitamin B12 levels did not show any significant difference between the two groups (p > .05), but interestingly, in patients with psoriasis, men had a significantly higher incidence of hyperhomocysteinemia and lower levels of erythrocyte folate (p = .14). Overall, there is no significant difference in serum levels of homocysteine and metabolic-related parameters between the case and control group. There was no significant relationship between the severity of psoriasis and the body mass index of patients (p > .05). CONCLUSION: Patients with psoriasis had a higher body mass index and higher levels of homocysteine in men. Hyperhomocysteinemia could be a predisposing factor of cardiovascular events, but more evaluations as a part of metabolic syndrome in patients with psoriasis are needed.