Schistosomiasis-associated pulmonary arterial hypertension: survival in endemic area in Brazil.

BACKGROUND: The survival of schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH) patients in endemic areas is unknown, but can be estimated using predictive equations. METHODS: We retrospectively analyzed all consecutive patients diagnosed with Sch-PAH referred to the Pronto SocorroCardiologico de Pernambuco between 2004 and 2010 using specific therapy and measured laboratory, diagnostic imaging, and baseline hemodynamic parameters. Observed and predicted survivals according to the National Institutes of Health (NIH) and Pulmonary Hypertension Connection (PHC) registry equations were compared by the Kaplan-Meier method, log-rank test and Cox proportional hazards model. RESULTS: Sixty-eight patients (47 [69.1%] women) observed for a mean of 3.1 years (range, 7-72 months), median survival was 74 months, and 42 (61.7%) survived. The sex and age distributions were similar for functional class I/II and III/IV patients. Hemodynamic abnormalities were severe: mean right atrial pressure, 12.6 ± 6.2 mmHg; mean pulmonary artery pressure, 60.3 ± 13.69 mmHg; pulmonary vascular resistance, 14.62 ± 7.04 Wood units; and cardiac index, 2.3 ± 0.8 L/min/m2. The usual idiopathic PAH predictors were not prognostic in Sch-PAH patients. The 1-, 3- and 5-year survival rates were 92.1%, 75.2%, and 50.8%, respectively, and those estimatedby the NIH and PHC registry equations were 68%, 45% and 32% (p = 0.001), and 93%, 79% and 68% (p = 0.340), respectively. CONCLUSIONS: Sch-PAH patients in endemic areas have severe hemodynamic profiles and reduced long-term survivaldespite treatment. The PHC registry equation may be a useful tool to estimate survival in Sch-PAH.

Reduced folate carrier-1 G80a gene polymorphism is associated with neuroblastoma's development.

Neuroblastoma is a malignant embryonal tumor of neural crest cells that give rise to the sympathetic nervous system, responsible for 10-70% of all cases of childhood cancer. Because of its early appearance, it has been suggested that risk factors active in the prenatal can be associated with the pathogenesis of neuroblastoma. The aim of this study was to investigate whether the genetic polymorphisms MTHFR C677T and A1298C, MTR A2756G, TYMS 2R/3R and SLC19A1 G80A, involved in folate metabolism, increase the risk of neuroblastoma in Brazilian children. This study comprised 31 Brazilian children (0-14 years old) diagnosed with neuroblastoma compared with 92 controls. Investigation of polymorphisms MTHFR C677T, MTR A2756G and SLC19A1 A80G was performed using PCR-RFLP, the TYMS 2R/3R using PCR and MTHFR A1298C using AS-PCR. The SLC19A1 A80A genotype was significantly associated with the development of neuroblastoma, compared with the control group (Williams G-Test = 0.0286; OR = 5.1667; 95% CI = 1.4481-18.4338; p = 0.0175). When analyzed together, the 80AG+AA genotypes showed a trend toward association (OR = 3.3033; 95% CI = 1.0586-10.3080; p = 0.0563). Our results suggest that individuals carriers of genotype AA for the SLC19A1 gene present risk for the development of neuroblastoma and possibly have difficulty in absorption of folic acid by the cells, and this may adversely affect the metabolism of folate causing genomic instability and promoting the development of cancer. This is the first retrospective/prospective study to examine the relationship between polymorphisms of folate pathway genes and risk of neuroblastoma.

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and high plasma homocysteine in chronic hepatitis C (CHC) infected patients from the Northeast of Brazil.

BACKGROUND/AIM: Hyperhomocysteinemia due to Methylenetetrahydrofolate Reductase (MTHFR) gene, in particular the C677T (Ala222Val) polymorphism were recently associated to steatosis and fibrosis. We analyzed the frequency of MTHFR gene in a cross-sectional study of patients affected by Chronic Hepatitis C (CHC) from Northeast of Brazil. METHOD: One hundred seven-four untreated patients with CHC were genotyped for the C677T MTHFR. Genomic DNA was extracted from peripheral blood cells and the C677T MTHFR polymorphism was identified by PCR-RFLP. The homocysteine (Hcy) levels were determined by chemiluminescence method. All patients were negative for markers of Wilson's disease, hemochromatosis and autoimmune diseases and have current and past daily alcohol intake less than 100 g/week. RESULTS: Among subjects infected with CHC genotype non-1 the frequency of MTHFR genotypes TT was 9.8% versus 4.4% genotype 1 (p = 0.01). Nevertheless, association was found between the MTHFR genotype TT × CT/CC polymorphism and the degree of steatosis and fibrosis in both hepatitis C genotype (p < 0.05). A significant difference was found on plasma Hcy levels in patients with steatosis regardless of HCV genotype (p = 0.03). CONCLUSION: Our results indicate that plasma Hcy levels is highly prevalent in subjects with chronic hepatits C with steatosis regardless of HCV genotype and vitamin deficiency. The presence of genotype TT of MTHFR C677T polymorphism was more common in CHC genotype non-1 infected patient regardless of histopathological classification and genotype TT+CT frequencies were significant in the presence of fibrosis grade 1+2 and of steatosis in CHC infected patients from the northeast of Brazil regardless of HCV genotype. The genetic susceptibility of MTHFR C677T polymorphism should be confirmed in a large population.