TNF-alpha and IL-8: serum levels and gene polymorphisms (-308G>A and -251A>T) are associated with classical biomarkers and medical history in children with sickle cell anemia.

Sickle cell anemia (SCA) is a disorder characterized by a heterogeneous clinical outcome. In the present study, we investigated the associations between Tumor Necrosis Factor-alpha (TNF-alpha) -308G>A and Interleukin 8 (IL-8) -251A>T gene polymorphisms, medical history and classical biomarkers in children with steady-state SCA. In total, 210 SCA patients aged 2-21 years and 200 healthy controls were studied. Gene polymorphisms, betaS-globin haplotypes and a 3.7-kb deletion in alpha2-thalassemia (α2-thal3.7 kb) were investigated by PCR/RFLP analysis, and cytokine levels were determined by ELISA. Splenomegaly (p=.032) was more prevalent among children younger than 5 years of age. The A allele of the TNF-alpha -308G>A gene polymorphism and the presence of α2-thal3.7 kb were associated with an increase risk of splenic sequestration events (p=.001; p=.046), while the T allele of the IL-8 -251A>T gene polymorphism was considered to be a protective factor for splenomegaly events (p=.032). Moreover, the A allele of the TNF-alpha -308G>A gene polymorphism was associated with high TNF-alpha levels (p=.021), and the hemoglobin F and hemoglobin S haplotypes were correlated with serum levels of IL-8. The logistic regression analysis showed significant effects of the TNF-alpha and IL-8 gene polymorphisms, beta(S)-globin gene haplotypes and α2-thal3.7 kb on the occurrence of splenic sequestration events. Our study emphasizes that the identification of new genetic and immunological biomarkers and their associations with classical markers is an important strategy to elucidate the underlying causes of different SCA phenotypes and their effects on patient outcome.

Folate, vitamin B12 and total homocysteine levels in neonates from Brazil.

OBJECTIVE: To determine folates, vitamin B12 and total homocysteine levels among neonates from mothers of low or high socioeconomic status. DESIGN: We carried out a cross-sectional transversal study comprising 143 neonates from two maternity hospitals in the city of Salvador, Northeast of Brazil. Cord blood samples were obtained at the time of delivery from newborns from low (group 1, n=77) or high (group 2, n=66) socioeconomic status. The vitamin B12 and folates were analyzed by electrochemiluminescence immunoassay and by a competitive test using a natural folate-binding protein (FBP), respectively. Total homocyteine levels were measured by fluorescence polarization immunoassay. Maternal environmental risk factors for pregnancy complications were obtained from all mothers. RESULTS: Only 2% of women from group 1 received prenatal care/vitamin supplementation, whereas almost all mothers from group 2 (96%) were properly followed. Anemia and/or infections pre- or during pregnancy was more prevalent among mothers of babies from group 1. Folate levels among newborns from group 1 and 2 were 7.38+/-2.71 and 8.83+/-4.06 ng/ml, respectively. No difference in the vitamin B12 levels was determined between groups. In addition, tHcy serum levels were higher among newborns from group 1 compared to those from group 2 (8.54+/-4.06 vs 6.35+/-1.33 micromol/l, respectively; P=0.005). CONCLUSION: These results demonstrate that unprivileged young woman has limited accesses to prenatal care, present high-risk factors that hamper both maternal and newborn health. Maternal and newborn health status could be improved by simply reinforcing the use of folate-enriched diet. The work presented illustrates the challenges that developing countries have to face in order to provide preventive adequate health care to the population at large.

alpha-Thalassemia 2, 3.7 kb deletion and hemoglobin AC heterozygosity in pregnancy: a molecular and hematological analysis.

alpha-Thalassemia is a synthesis hemoglobinopathy with a worldwide distribution. alpha-thalassemia-23.7kb (alpha-Thal23.7kb) was investigated by PCR and standard hematologic analysis techniques in 106 pregnant women - 53 heterozygous for hemoglobin (Hb) A and C (AC) and 53 homozygous for the normal Hb A (AA) with similar ages and race ancestry. Eleven (21%) of AC women were alpha-Thal23.7kb heterozygous and 1 (2%) was homozygous, while 12 AA women (23%) were heterozygous. In the AA group, the MCV differed among those with normal alpha genes and those with alpha-Thal23.7kb (P = 0.031). Statistical analysis of AC group patients with normal alpha genes and alpha-Thal23.7kb carriers showed differences in MCV (P = 0.001); MCH (P = 0.003) and Hb C concentrations (P = 0.011). Analysis of AA and AC group patients with normal alpha genes showed differences in RBC (P = 0.033), Hb concentration (P = 0.003) and MCHC (P < 0.0001). There were no statistically significant differences for any hematologic parameters between AC and AA group patients with the alpha-Thal23.7kb genotype. The AC alpha-Thal23.7kb homozygous women had low hematologic parameters. Serum ferritin levels were normal among the groups studied. These results emphasize the importance of diagnosis and follow-up of patients with hemoglobinopathy carriers during pregnancy in order to administer adequate therapy and avoid further complications for mothers and newborns.