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.

Role of adiponectin, resistin and monocyte chemo-attractant protein-1 in overweight/obese asthma phenotype in children.

BACKGROUND: Asthma is a chronic inflammatory disorder of the airways with diverse overlapping pathologies and phenotypes contributing to a significant heterogeneity in clinical manifestations. Obesity may modify asthma risk, phenotype, and prognosis. A suggested mechanism linking obesity and asthma is through systemic inflammation. Adipokines secreted by adipose tissue were suggested to provide a link between obesity and asthma. OBJECTIVE: To have an understanding for the contribution of adiponectin, resistin and MCP-1 to development of distinct asthma phenotype in overweight/obese children through assessment of their serum level and correlation to pulmonary function tests. SUBJECTS AND METHODS: The study included 29 normal weight asthmatics, 23 overweight/obese asthmatic children and 30 controls. All cases were subjected to detailed history taking, thorough examination and pulmonary function tests. Serum adiponectin, resistin, MCP-1 and IgE were assessed to all recruited subjects. RESULTS: Adiponectin level was significantly higher in overweight/obese asthmatics (24900 ± 1600 ng/ml) compared to normal weight asthmatics (21700 ± 1700 ng/ml) and control (23000 ± 3200 ng/ml), (p < 0.001 & 0.051 respectively). Normal weight asthmatics had significantly lower adiponectin level than control, (p = 0.039). A significant low level of MCP-1 in overweight/obese asthmatics (149.5 (20-545) ng/L) compared to control (175 (28 -1123.5) ng/L), p = 0.037. No significant difference was found regarding resistin. Normal weight asthmatics had significantly lower FEV1% and FVC% compared to overweight/obese asthmatics (p = 0.036, 0.016 respectively). A significant positive correlation was found between (FEV1%, FVC) and BMI in normal weight asthmatics (P = 0.01, < 0.01 respectively) and a significant negative correlation between PEF and BMI (-0.42, p = 0.05) in obese/overweight asthmatics. Resistin/adiponectin ratio was not affected by sex, degree of asthma severity or level of asthma control in either normal weight or overweight/obese asthmatic. CONCLUSION: This work could suggest that adiponectin may play a role in overweight/obese asthma phenotype where it is possible to have a dual action (pro & anti- inflammatory). It seems that resistin had no role in asthma pathogenesis.

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.

Assessment of serum level of corticotropin-releasing factor in primary nocturnal enuresis.

INTRODUCTION: Primary nocturnal enuresis is one of the sleep related phenomena characterized by disruption in the relationship between arousal and urination. Corticotropin-releasing factor (CRF) is a neurohormone released from the paraventricular nucleus of the hypothalamus into the median eminence to elicit release of adrenocorticotrophin from the anterior pituitary. It may act to modulate autonomic function and behavior in concert with the endocrine effects. Conflicting animal studies about the role of CRF in micturition, either facilitating or inhibiting, have been raised. It was suggested to be a novel target for treatment of urinary disorders based on the finding that manipulation of CRF in the pontine micturition circuit could affect urodynamic function. AIM: The aim was to throw light on the possible role of CRF in primary monosymptomatic nocturnal enuresis by assessing its serum level. SUBJECTS AND METHODS: Twenty-nine children aged 8-14 years complaining of primary monosymptomatic nocturnal enuresis and 16 age- and sex-matched healthy children with good toilet control day and night were recruited to the study. History taking, clinical examination, and assessment of serum CRF levels in the morning and evening (9 a.m. and 9 p.m.) were carried out for all patients and controls. RESULTS AND DISCUSSION: A positive family history of enuresis was detected in 82.8% of enuretic patients. Serum levels of CRF (both morning and evening) were significantly lower in patients than in controls. Several animal studies suggested that CRF in descending projections from Barrington's nucleus to the lumbosacral parasympathetic neurons is inhibitory to micturition, which supports our results and the assumption that reduction of the evening serum CRF level could have a role in the occurrence of primary monosymptomatic nocturnal enuresis. No significant difference was found between morning and evening CRF serum levels in either cases or controls, which negates our assumption of having a rhythmic pattern of release (figure). No correlations with age were found. According to their history, all our enuretic patients were deep sleepers. Deep sleep and difficult arousal were found to have a major role in primary monosymptomatic nocturnal enuresis. It was proposed that CRF function may allow arousal to occur before micturition to facilitate preparative behaviors. A lower CRF level may explain deep-sleep pattern in children with enuresis. CONCLUSION: CRF was deficient in our enuretic children, which may draw attention to the possible pathophysiological implications in primary nocturnal enuresis (either at the level of loss of inhibitory effect on micturition or lack of arousal in response to bladder distension). Further proof studies are recommended.

Adipokines Vaspin and Visfatin in Obese Children.

BACKGROUND: Adipokines provides new insights about the physiology, pathology and treatment of obesity. AIM: We investigated the association between serum vaspin and serum visfatin concentrations with obesity in Egyptian children. MATERIAL AND METHODS: Twenty two obese children with body mass index (BMI) above 95th percentile; 11 males and 11 females were included in this study. Their mean age was 9.18 ± 2.8 years. After general clinical examination, fasting blood glucose, triglycerides, total cholesterol and high density lipoprotein cholesterol were measured in cases and controls (n=11). Fasting insulin, vaspin and visfatin were detected using ELIZA. Insulin resistance was estimated by Homeostasis model assessment method (HOMA-IR). RESULTS: Blood pressure, in both systolic and diastolic measurements was elevated significantly in obese children. Significant elevation of serum insulin and insulin resistance (HOMA/IR) were observed in obese children too. Vaspin and visfatin showed significant elevation in obese children than controls. Significant positive correlations were detected between visfatin and BMI, waist circumference, hip circumference and HOMA/IR. We found that Vaspin and visfatin are higher in obese children. CONCLUSION: Visfatin but not vaspin correlates positively with waist circumference and HOMA/IR in obese children.

Anti-diuretic hormone and genetic study in primary nocturnal enuresis.

OBJECTIVE: To investigate whether primary nocturnal enuresis (PNE) is related to a disturbance in anti-diuretic hormone (ADH) secretion pattern at night which may be genetically inherited. SUBJECTS AND METHODS: This study included 121 children aged 6-18 years with PNE and 45 matched healthy children as controls. Enuretic children were subjected to genetic evaluation and cytogenetic assessment (n = 99). Assay of ADH levels (9-11 am & 9-11 pm) was performed for cases (n = 99) and controls. RESULTS: There was a positive family history in 82.4% (autosomal dominant in 35.4% and autosomal recessive in 64.6%). ADH morning and evening values were reversed in cases vs controls with significant difference in morning level. Reversal of circadian rhythm was present in 71.7% of cases and normal rhythm in 28.3% of them. Morning and evening ADH levels revealed significant difference between patients with reversed rhythm and those with normal one, and with controls. Mode of inheritance had no influence on hormonal level. Chromosomal abnormality was detected in 3 cases with reversed ADH rhythm, involving chromosome 22 in two of them. CONCLUSION: PNE could be attributed in part to reversed ADH circadian rhythm which may be linked to chromosome 22.