Interleukin 17F Gene Polymorphism as a Potential Protective Factor in the Immunopathology of Ocular Toxoplasmosis.

Ocular toxoplasmosis (OT) is characterised by intraocular inflammation due to Toxoplasma gondii infection. Studies have found that interleukin 17 (IL-17) plays a central role in the pathology of OT. However, nucleotide variability in IL17 and interleukin 17 receptor (IL17R) genes has not been characterised in OT. As cytokine gene polymorphisms may influence the expression of these molecules, the aim of this study was to verify whether IL17A (rs2275913), IL17F (rs763780), IL17RA (rs4819554) and IL17RC (rs708567) polymorphisms are associated with OT in a Brazilian population. This study enrolled 214 patients seropositive for T. gondii (110 with OT and 104 without) and 107 controls. Polymorphisms were identified by PCR-restriction fragment length polymorphism analysis, validated by DNA sequencing with chi-square and multivariate analyses being used to assess possible associations between polymorphisms and OT. Logistic regression under the dominant model revealed a protection factor against OT of the C mutant allele of the IL17F (rs763780) polymorphism. The T/C-C/C genotypes were significantly more common in patients without OT compared to those with OT (p value = 0.0066) and controls (p value = 0.014). Findings from this study suggest that the IL17F polymorphism may have an influence in the immunopathology of OT in Brazilian individuals.

Association of FOXO3 polymorphism (rs3800231) and clinical subphenotypes of beta thalassemic individuals

Abstract Introduction Studies have shown that the loss of the FOXO3 transcriptional function is involved in the pathophysiology of some chronic erythroid disorders, including beta-thalassemia (β-thal). Therefore, the single nucleotide polymorphism (SNP) rs3800231 (35-2764A > G) could contribute to alterations in its transcriptional activity, acting as a modifier of β-thal phenotypic manifestations. Objective and method In order to better understand the genotypic and/or allelic distributions among β-thal patients, we evaluated 83 β-thal heterozygous and 20 homozygous, compared to 117 individuals without hemoglobinopathies (control group). Additionally, we verified any influence of the FOXO3 polymorphism on clinical manifestations among β-thal homozygotes. Results We obtained higher frequencies of the wild-type homozygous (AA) and the wild-type allele (A) in the β-thal group (p< 0.0001 and p= 0.00014, respectively). The most common clinical manifestations found among β-thal homozygotes were iron overload (90%), splenomegaly (65%) and bone complications (35%), e.g., osteopenia/osteoporosis. We observed that close to 80% of the patients presenting such manifestations had the genotype AA. However, we did not find any significant involvement of the FOXO3 polymorphism in clinical manifestation occurrences. Conclusion Thus, we concluded that the SNP rs3800231 did not play a significant role as a modifier of the clinical manifestations observed in the β-thal homozygotes studied.

Association of FOXO3 polymorphism (rs3800231) and clinical subphenotypes of beta thalassemic individuals.

INTRODUCTION: Studies have shown that the loss of the FOXO3 transcriptional function is involved in the pathophysiology of some chronic erythroid disorders, including beta-thalassemia (ß-thal). Therefore, the single nucleotide polymorphism (SNP) rs3800231 (35-2764A > G) could contribute to alterations in its transcriptional activity, acting as a modifier of ß-thal phenotypic manifestations. OBJECTIVE AND METHOD: In order to better understand the genotypic and/or allelic distributions among ß-thal patients, we evaluated 83 ß-thal heterozygous and 20 homozygous, compared to 117 individuals without hemoglobinopathies (control group). Additionally, we verified any influence of the FOXO3 polymorphism on clinical manifestations among ß-thal homozygotes. RESULTS: We obtained higher frequencies of the wild-type homozygous (AA) and the wild-type allele (A) in the ß-thal group (p < 0.0001 and p = 0.00014, respectively). The most common clinical manifestations found among ß-thal homozygotes were iron overload (90%), splenomegaly (65%) and bone complications (35%), e.g., osteopenia/osteoporosis. We observed that close to 80% of the patients presenting such manifestations had the genotype AA. However, we did not find any significant involvement of the FOXO3 polymorphism in clinical manifestation occurrences. CONCLUSION: Thus, we concluded that the SNP rs3800231 did not play a significant role as a modifier of the clinical manifestations observed in the ß-thal homozygotes studied.

A interação entre Hb B2, Hb S e beta talassemia: um relato de caso familiar

As hemoglobinopatias são doenças hereditárias que incluem talassemia e doença falciforme. O objetivo do presente estudo foi destacar a interação entre a variante Hb S, formas talassêmicas (beta talassemia por IVS1-6) e a variante Hb B2. Os exames realizados foram hemograma completo, eletroforese de hemoglobina em pH ácido e alcalino, dosagem de hemoglobina A2, Cromatografia Líquida de Alta Performance e investigação molecular. Esse relato evidencia a interação entre os polimorfismos de hemoglobina na população brasileira e a necessidade de adequada interpretação dos resultados de testes clássicos para a melhor compreensão dos casos.

Hemoglobinopathies are a hereditary disease that includes thalassemia and sickle cell disease. The present study aimed to show the interaction between the Hb S variant, thalassemia forms (Beta-thalassemia by IVS1-6), and the Hb B2 variant. The tests performed were complete blood count, hemoglobin electrophoresis at acid and alkaline pH, hemoglobin A2 dosage, High-Performance Liquid Chromatography, and molecular investigation. This report highlights the interaction between hemoglobin polymorphisms in the Brazilian population and the need for an adequate interpretation of the results of classical tests for a better understanding of the cases.

Association of HMIP1 C-893A polymorphism and disease severity in patients with sickle cell anemia

Abstract Introduction: Sickle cell anemia (SCA) is a Mendelian disorder with a heterogeneous clinical course. The reasons for this phenotypic diversity are not entirely established, but it is known that high fetal hemoglobin levels lead to a milder course of the disease. Additionally, genetic variants in the intergenic region HBS1L-MYB promote high levels of fetal hemoglobin into adulthood. Objective: In the present study, we investigated the HMIP1 C-839A (rs9376092) polymorphism, located at the HBS1L-MYB intergenic region block 1, in SCA patients. Method: We analyzed 299 SCA patients followed in two reference centers in Brazil. The HMIP1 C-839A (rs9376092) genotypes were determined by allele specific polymerase chain reactions. Clinical and laboratory data were obtained from patient interviews and medical records. Results: The median fetal hemoglobin levels were higher in patients with the HMIP1 C-839A (rs9376092) AA genotype (CC = 6.4%, CA = 5.6% and AA = 8.6%), but this difference did not reach significance (p = 0.194). No association between HMIP1 C-839A (rs9376092) genotypes and other clinical and laboratorial features was detected (p > 0.05). Conclusion: In summary, our data could not support the previously related association between the HMIP1 C-893A (rs9376092) polymorphism and differential fetal hemoglobin levels.

Association of HMIP1 C-893A polymorphism and disease severity in patients with sickle cell anemia.

INTRODUCTION: Sickle cell anemia (SCA) is a Mendelian disorder with a heterogeneous clinical course. The reasons for this phenotypic diversity are not entirely established, but it is known that high fetal hemoglobin levels lead to a milder course of the disease. Additionally, genetic variants in the intergenic region HBS1L-MYB promote high levels of fetal hemoglobin into adulthood. OBJECTIVE: In the present study, we investigated the HMIP1 C-839A (rs9376092) polymorphism, located at the HBS1L-MYB intergenic region block 1, in SCA patients. METHOD: We analyzed 299 SCA patients followed in two reference centers in Brazil. The HMIP1 C-839A (rs9376092) genotypes were determined by allele specific polymerase chain reactions. Clinical and laboratory data were obtained from patient interviews and medical records. RESULTS: The median fetal hemoglobin levels were higher in patients with the HMIP1 C-839A (rs9376092) AA genotype (CC=6.4%, CA=5.6% and AA=8.6%), but this difference did not reach significance (p=0.194). No association between HMIP1 C-839A (rs9376092) genotypes and other clinical and laboratorial features was detected (p>0.05). CONCLUSION: In summary, our data could not support the previously related association between the HMIP1 C-893A (rs9376092) polymorphism and differential fetal hemoglobin levels.

Polymorphism in the IL-1ß promoter is associated with IgG antibody response to circumsporozoite protein repeats of Plasmodium vivax.

BACKGROUND: It is well established that infection by Plasmodium vivax is a result of host-parasite interactions. In the present study, association with the IL1/IL2 cytokine profiles, anticircumsporozoite protein antibody levels and parasitic loads was evaluated in individuals naturally infected with P. vivax in an endemic area of the Brazilian Amazon. METHODS: Molecular diagnosis of P. vivax and variants was performed using the PCR-RFLP method and IL1B -511C>T, IL2 -330T>G and IL2+114T>G polymorphisms were identified using PCR-RFLP and allele-specific PCR. IL-1ß and IL-2 cytokine levels were detected by flow cytometry and circumsporozoite protein (CSP) antibodies were measured by ELISA. RESULTS: Three variants of P. vivax CSP were identified and VK247 was found to be the most frequent. However, the prevalence and magnitude of IgG antibodies were higher for the VK210 variant. Furthermore, the antibody response to the CSP variants was not associated with the presence of the variant in the infection. Significant differences were observed between the single nucleotide polymorphism (SNP) -511T>C in the IL1B gene and levels of antibodies to the VK247 and P. vivax-like variants, but there were no associations between SNPs in IL1 and IL2 genes and their plasma products. CONCLUSIONS: Individuals with the rs16944 CC genotype in the IL1ß gene have higher antibody levels to the CSP of P. vivax of VK247 and P. vivax-like variants.

Whole-genome duplication and hemoglobin differentiation traits between allopatric populations of Brazilian Odontophrynus americanus species complex (Amphibia, Anura).

Two allopatric populations of Brazilian diploid and tetraploid Odontophrynus americanus species complex, both from São Paulo state, had their blood hemoglobin biochemically analyzed. In addition, these specimens were cytogenetically characterized. Biochemical characterization of hemoglobin expression showed a distinct banding pattern between the allopatric specimens. Besides this, two distinct phenotypes, not linked to ploidy, sex, or age, were observed in adult animals of both populations. Phenotype A exhibits dark-colored body with small papillae, ogival-shaped jaw with reduced interpupillary distance and shorter hind limbs. Phenotype B shows yellowish-colored body with larger papillae, arch-shaped jaw with broader interpupillary distance and longer hind limbs. Intermediate phenotypes were also found. Considering the geographical isolation of both populations, differences in chromosomal secondary constrictions and distinct hemoglobins banding patterns, these data indicate that 2n and 4n populations represent cryptic species in the O. americanus species complex. The observed phenotypic diversity can be interpreted as population genetic variability. Eventually future data may indicate a probable beginning of speciation in these Brazilian frogs. Such inter- and intrapopulational differentiation/speciation process indicates that O. americanus species complex taxonomy deserves further evaluation by genomics and metabarcoding communities, also considering the pattern of hemoglobin expression, in South American frogs.

Impaired antioxidant capacity causes a disruption of metabolic homeostasis in sickle erythrocytes.

This study examined particularly relevant redox pathways such as glycolysis, pentose phosphate pathway (PPP), metHb reductase and nucleotide metabolism, in order to better address how sickle cells deal with redox metabolism disruption. We also investigated the generation of specific oxidative lesions, and the levels of an unexplored antioxidant that could act as a candidate biomarker for oxidative status in sickle cell anemia (SCA). We adopted rigorous exclusion criteria to obtain the studied groups, which were composed by 10 subjects without hemoglobinopathies and 10 SCA patients. We confirmed that sickle cells overwhelm the antioxidant defense system, leading to an impaired antioxidant capacity that significantly contributed to the increase in cholesterol oxidation (ChAld) and hemolysis. Among the antioxidants evaluated, ergothioneine levels decreased in SCA (two-fold). We found strong correlations of ergothioneine levels with other erythrocyte metabolism markers, suggesting its use as an antioxidant therapy alternative for SCA treatment. Moreover, we found higher activities of MetHb reductase, AChE, G6PDH, HXK, and LDH, as well as levels of NADPH, ATP and hypoxanthine in sickle cells. On this basis, we conclude that impaired antioxidant capacity leaves to a loss of glycolysis and PPP shifting mechanism control and further homeostasis rupture, contributing to a decreased lifespan of sickle cells.

Atypical ß-S haplotypes: classification and genetic modulation in patients with sickle cell anemia.

ß-S globin haplotype (ßS haplotype) characterization in sickle cell anemia (SCA) patients is important because it assists individualized treatment. However, the patient with atypical haplotypes do not present detailed studies such as clinical and laboratory data. To understand the phenotypic expression of atypical haplotype patients in relation to typical haplotype ones, it may be necessary to assess the main clinical and laboratorial parameters and investigate transcription factors, as possible genetic modulators that can contribute to the improvement of the SCA patients' clinical condition. The study group was composed of 600 SCA Brazilian patients of both genders ranging in age from 1 to 68 years. The atypical haplotypes were the third most frequent (5.7%) with 11 patterns numerically ranked according to occurrence. We verified that patients with atypical 1 haplotype in combination with Bantu haplotype presented milder clinical outcomes in relation to Bantu/Bantu and Benin/Benin patients, according to improved values of hemoglobin and hematocrit. In clinical severity, we did not observe significant statistical differences between typical and atypical haplotype patients, and this result can be explained with reference to the action of transcription factors in ß-globin cluster. Thus, we presented the atypical haplotype relationship with SCA pathophysiology, reinforcing the hypothesis that individual genetic factors may be responsible for phenotypic diversity of the disease.

Whole-genome duplication and hemoglobin differentiation traits between allopatric populations of Brazilian Odontophrynus americanus species complex (Amphibia, Anura)

Two allopatric populations of Brazilian diploid and tetraploid Odontophrynus americanus species complex, both from São Paulo state, had their blood hemoglobin biochemically analyzed. In addition, these specimens were cytogenetically characterized. Biochemical characterization of hemoglobin expression showed a distinct banding pattern between the allopatric specimens. Besides this, two distinct phenotypes, not linked to ploidy, sex, or age, were observed in adult animals of both populations. Phenotype A exhibits dark-colored body with small papillae, ogival-shaped jaw with reduced interpupillary distance and shorter hind limbs. Phenotype B shows yellowish-colored body with larger papillae, arch-shaped jaw with broader interpupillary distance and longer hind limbs. Intermediate phenotypes were also found. Considering the geographical isolation of both populations, differences in chromosomal secondary constrictions and distinct hemoglobins banding patterns, these data indicate that 2n and 4n populations represent cryptic species in the O. americanus species complex. The observed phenotypic diversity can be interpreted as population genetic variability. Eventually future data may indicate a probable beginning of speciation in these Brazilian frogs. Such inter- and intrapopulational differentiation/speciation process indicates that O. americanus species complex taxonomy deserves further evaluation by genomics and metabarcoding communities, also considering the pattern of hemoglobin expression, in South American frogs.

Whole-genome duplication and hemoglobin differentiation traits between allopatric populations of Brazilian Odontophrynus americanus species complex (Amphibia, Anura)

Two allopatric populations of Brazilian diploid and tetraploid Odontophrynus americanus species complex, both from São Paulo state, had their blood hemoglobin biochemically analyzed. In addition, these specimens were cytogenetically characterized. Biochemical characterization of hemoglobin expression showed a distinct banding pattern between the allopatric specimens. Besides this, two distinct phenotypes, not linked to ploidy, sex, or age, were observed in adult animals of both populations. Phenotype A exhibits dark-colored body with small papillae, ogival-shaped jaw with reduced interpupillary distance and shorter hind limbs. Phenotype B shows yellowish-colored body with larger papillae, arch-shaped jaw with broader interpupillary distance and longer hind limbs. Intermediate phenotypes were also found. Considering the geographical isolation of both populations, differences in chromosomal secondary constrictions and distinct hemoglobins banding patterns, these data indicate that 2n and 4n populations represent cryptic species in the O. americanus species complex. The observed phenotypic diversity can be interpreted as population genetic variability. Eventually future data may indicate a probable beginning of speciation in these Brazilian frogs. Such inter- and intrapopulational differentiation/speciation process indicates that O. americanus species complex taxonomy deserves further evaluation by genomics and metabarcoding communities, also considering the pattern of hemoglobin expression, in South American frogs.

The relationship between of ACE I/D and the MTHFR C677T polymorphisms in the pathophysiology of type 2 diabetes mellitus in a population of Brazilian obese patients.

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.

Effects of benzo[a]pyrene on the blood and liver of Physalaemus cuvieri and Leptodactylus fuscus (Anura: Leptodactylidae).

Benzo[a]pyrene (BaP) is a bio-accumulative toxic compound found in the atmosphere, water, and soil that may affect the life cycle of amphibians. In this study, a few contamination biomarkers, such as hepatic melanomacrophages (MMs), mast cells, erythrocyte micronuclei (MN) and white blood cells were used to determine how BaP acts in these cells in the anurans Physalaemus cuvieri and Leptodactylus fuscus. Animals of both species were divided into three treatment groups: 1 day, 7 days and 13 days, subcutaneously injected 2 mg/kg BaP diluted in mineral oil and control group with only mineral oil. After 7 days, BaP caused the frequency of MN to increase in both species while reducing melanin area. The micronucleus frequency increased due to the genotoxicity of BaP, while the decreasing melanin area may be related to the inhibition of tyrosinase activity, an enzyme responsible for regulating melanogenesis, decreasing the synthesis of melanin. The mast cell density increased in all groups and in both species as a response to the inflammatory action of BaP. These cells respond to nonspecific inflammatory effects leading, therefore, to this response in all treatments. The percentage of leukocytes remained unchanged probably due to great intraspecific variability. Additionally, the leukocyte profiles of both species were characterized and the differences were attributed to extrinsic factors. In short, BaP can affect the integrity of several organs and tissues, and cell functions leading to the conclusion that this compound is hepatotoxic, genotoxic and immunotoxic for anurans.

The relationship between of ACE I/D and the MTHFR C677T polymorphisms in the pathophysiology of type 2 diabetes mellitus in a population of Brazilian obese patients

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.

Anti-Toxoplasma gondii antibodies in patients with beta-hemoglobinopathies: the first report in the Americas.

BACKGROUND: In Brazil, there have been no previous studies of Toxoplasma gondii infection in sickle cell anemia patients and carriers of severe forms of beta-thalassemia. This study evaluated T. gondii infection in patients with beta-hemoglobinopathies. METHODS: A total of 158 samples, 77 (48.7%) men and 81 (51.3%) women, were evaluated. Three groups were formed: G1 (85 patients with sickle cell disease); G2 (11 patients with homozygous beta-thalassemia; G3 (62 patients with heterozygous beta-thalassemia). ELISA was employed to identify anti-T. gondii IgM and IgG antibodies, and molecular analysis was performed to determine beta-hemoglobin mutations. Fisher's exact test was used to compare frequencies of anti-T. gondii IgM and IgG antibodies in respect to gender and age. RESULTS: Anti-T. gondii IgG antibodies were found in 43.5% of individuals in G1, 18.1% in G2 and 50% in G3. All samples from G1 and G2 were seronegative for anti-T. gondii IgM antibodies, but 3.2% from G3 were seropositive. Considering anti-T. gondii IgG antibodies, no statistical significant differences were found between these groups nor in seroprevalence between genders within each group. Despite this, comparisons of the mean ages between G1, G2 and G3 were statistically significant (G2 vs. G1: p value = 0.0001; G3 vs. G1: p-value <0.0001; G3 vs. G2: p-value = 0.0001). CONCLUSION: A comparison by age of patients with sickle cell anemia showed a trend of lower risk of infection among younger individuals. Therefore, this study demonstrates that T. gondii infection occurs in patients with beta-thalassemia and sickle cell anemia in Brazil as seen by the presence of anti-T. gondii IgM and IgG antibodies.

Mutational Profile of Homozygous ß-Thalassemia in Rio de Janeiro, Brazil.

ß-Thalassemia (ß-thal) is a hemolytic anemia that is caused by point mutations in most cases. The Brazilian population is highly heterogeneous and knowledge of the mutations that make up the genotypic profile of individuals can contribute information about the formation of the population and clinical condition of patients. In this study, we evaluated the mutations present in homozygous ß-thal patients from Rio de Janeiro, Brazil. We analyzed 24 samples of peripheral blood of patients with homozygous ß-thal. To identify the mutations, we carried out allele-specific-polymerase chain reaction (AS-PCR) and DNA sequencing. We found 11 different mutations on the ß-globin gene. Among the most frequent mutations observed were HBB: c.92 + 6T>C, followed by HBB: c.93-21G>A, HBB: c.118C>T and HBB: c.92 + 1G>A. We also identified the rare mutation HBB: c.75T>A that was reported in an individual carrying Hb S (HBB: c.20A>T)/ß-thal (HBB: c.75T>A) but not in Brazilian thalassemic patients, thus, this is the first report of this mutation in Brazilian ß-thal patients. For its multiethnic character, Brazil has different mutations that cause ß-thal and that are distributed with different frequencies according to the regions of the country. Our findings contribute to the description of the mutational profile of Brazilian thalassemic patients, showing wide heterogeneity and genetic variability.

Impact of genetic polymorphisms in key enzymes of homocysteine metabolism on the pathophysiology of sickle cell anemia.

This work aimed at studying a possible influence of methylenetetrahydrofolate reductase (MTHFR; c. 677C>T) and cystathionine ß-synthase (CBS; 844ins68) polymorphisms on overall oxidative status of sickle cell anemia (SCA) patients and on routine markers, correlating them with hydroxycarbamide (HC) treatment. We evaluated 95 unrelated and diagnosed SCA patients. All patients received a prophylactic treatment with folic acid of 5mg/day, while 41 (43.2%) of them were under hydroxycarbamide (HC) treatment (average dose: 22mg/kg/day). MTHFR and CBS polymorphisms were identified by Polymerase Chain Reaction. Biochemical parameters were measured using spectrophotometric and chromatographic methods. Routine markers were developed by specialized laboratory. We did not find any effect of 677T and "I" allele combination on the biomarkers evaluated. On the other hand, MTHFR 677T mutation was related to a depletion of antioxidant capacity, according to the decreased catalase activity and a reduction about 30% of glutathione levels. Moreover, the presence of the insertion was related to about 23% less biomolecule oxidation levels and lower monocytes count, but about 14% higher lactate dehydrogenase activity. These findings may contribute to highlight that the MTHFR and CBS polymorphisms involvement in SCA pathophysiology is likely to be far more complex than it was explored to date.

Correction: Inflammation in Sickle Cell Disease: Differential and Down-Expressed Plasma Levels of Annexin A1 Protein.

[This corrects the article DOI: 10.1371/journal.pone.0165833.].