The association of TMPRSS6 gene polymorphism with iron status in Egyptian children (a pilot study).

Several studies have shown association of single nucleotide polymorphisms (SNPs) of hepcidin regulatory pathways genes with impaired iron status. The most common is in the TMPRSS6 gene. In Africa, very few studies have been reported. We aimed to investigate the correlation between the common SNPs in the transmembrane protease, serine 6 (TMPRSS6) gene and iron indicators in a sample of Egyptian children for identifying the suitable candidate for iron supplementation.Patients and methods One hundred and sixty children aged 5-13 years were included & classified into iron deficient, iron deficient anemia and normal healthy controls. All were subjected to assessment of serum iron, serum ferritin, total iron binding capacity, complete blood count, reticulocyte count, serum soluble transferrin receptor and serum hepcidin. Molecular study of TMPRSS6 genotyping polymorphisms (rs4820268, rs855791 and rs11704654) were also evaluated.Results There was an association of iron deficiency with AG of rs855791 SNP, (P = 0.01). The minor allele frequency for included children were 0.43, 0.45 & 0.17 for rs4820268, rs855791 & rs11704654 respectively. Genotype GG of rs4820268 expressed the highest hepcidin gene expression fold, the lowest serum ferroportin & iron store compared to AA and AG genotypes (p = 0.05, p = 0.05, p = 0.03 respectively). GG of rs855791 had lower serum ferritin than AA (p = 0.04), lowest iron store & highest serum hepcidin compared to AA and AG genotypes (p = 0.04, p = 0.01 respectively). Children having CC of rs11704654 had lower level of hemoglobin, serum ferritin and serum hepcidin compared with CT genotype (p = 0.01, p = 0.01, p = 0.02) respectively.Conclusion Possible contribution of SNPs (rs855791, rs4820268 and rs11704654) to low iron status.

Low Dose Iron Therapy in Children with Iron Deficiency: DNA Damage and Oxidant Stress Markers.

Conflicting data are available regarding oral iron therapy in iron deficiency (ID), iron deficiency anemia (IDA) and its relation to DNA damage, oxidative stress and antioxidant markers. Our aim was assessment of DNA damage, oxidative stress and anti-oxidant markers in children with ID and IDA before and after low dose iron therapy. The study was conducted in two stages, first stage was assessment of DNA damage using comet assay, malondialdehyde (MDA) and anti-oxidant enzymes levels (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) & total antioxidant capacity (TAC) in thirty-nine children with IDA, forty-five children with ID without anemia and sixty healthy controls. Second stage was assessment of previous markers together with hematological response following oral therapy with 10 mg/day ferric ammonium citrate for 8 weeks. Before treatment, there was no significant difference between the three groups regarding MDA, GPx, SOD, CAT and TAC. A significant increase was detected in the DNA damage in the 2 groups compared to control (p < 0.005). Following iron therapy, hematological parameters was improved together with a significant increase in GPx (P = 0.04), SOD (p = 0.002), TAC (P = 0.001) and non-significant reduction in DNA damage in IDA group. There was a significant increase in SOD (p = 0.001) & TAC (p = 0.001) and significant decrease in DNA damage (p = 0.001) in ID group. Low dose iron therapy could be sufficient to improve antioxidant status and DNA damage together with correction of hematologic indices.

Levels of cystatin C in low- and high-flux hemodialysis in children with end-stage renal disease.

BACKGROUND: Cystatin-C (CyC) is a middle molecule that is freely filtered at the glomerulus and almost completely reabsorbed by the proximal tubules. The aim of this study was to evaluate serum CyC and its reduction ratio as a biomarker for assessing the adequacy of the hemodialysis (HD) sessions in children with end-stage renal disease on maintenance HD. We also compared levels of CyC in patients on low-flux HD (LFH) and high-flux HD (HFH). METHODS: Forty patients were included in the study and divided into two groups, with one group (16 patients) receiving HFH and the other group receiving LFH (24 patients) (high-flux and low-flux polysulfone filters, respectively). Before and after each dialysis session serum CyC and beta-2-microglobulin (B2M) levels were measured using an ELISA technique, and routine laboratory tests were performed for each patient. RESULTS: Pre-dialytic levels of CyC were significantly lower in the patients receiving HFH than in those receiving LFH (7.33 ± 1.35 vs. 9.73 ± 0.93, respectively; p < 0.0001). In the HFH group, post-dialytic levels of serum CyC were significantly lower than pre-dialytic levels (4.49 ± 0.71 vs. 7.33 ± 1.35, respectively; p < 0.0001). The reduction ratio (RR) of CyC was significantly higher in the HFH group than in the LFH group (38.2 ± 3.91 vs. -6.49 ± 5.05, respectively; p < 0.0001). Serum CyC level significantly correlated with B2M, urea and creatinine levels in both the LFH and HFH groups, whereas its RR significantly correlated with the RRs of urea, creatinine, and B2M in the HFH group. CONCLUSION: The results of our study emphasize the role of CyC as a good marker for assessing the adequacy of HD sessions in children on HFH and show that the CyC RR may be used as an index of middle-molecule toxin clearance following HFH sessions.