Study of the effect of ACYP2 single nucleotide polymorphisms rs843711 and rs843706 in Egyptian patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a multifactorial disease with both genetic and environmental factors contributing to its pathogenesis. ACYP2 is a gene that is related to cell differentiation, apoptosis and prevention of malignant tumors. The ACYP2 gene also affects telomere length. The aim of this study was to evaluate the association between ACYP2 single nucleotide polymorphisms (SNPs) (rs843711), and (rs843706) and incidence of HCC in Egyptian HCC patients. The study included 30 patients with HCC and 30 normal controls. Detection of ACYP2 gene SNPs rs843711, and rs843706 in all study participants was done using real time polymerase chain reaction (RT-PCR). The results showed that all participants including HCC patients and controls carried the heterozygous CA (100%) of the rs843706 SNP (p> 0.05). As for the rs843711, 3.3% of HCC patients had the homozygous TT genotype, 46.7% had the heterozygous CT genotype and 50% had the wild CC genotype, while in the control group, 60% had the heterozygous CT genotype and 40% had the wild CC genotype with no significant difference between both groups (p>0.05). We concluded that there was no association between SNPs ACYP2 rs843706 and rs843711 and occurrence of HCC.

Anti-Müllerian hormone levels in patients with turner syndrome: Relation to karyotype, spontaneous puberty, and replacement therapy.

Most girls with Turner syndrome (TS) suffer from incomplete sexual development, premature ovarian failure, and infertility due to abnormal ovarian folliculogenesis. Serum anti-Müllerian hormone (AMH) levels reflect the ovarian reserve in females, even in childhood. Thus, we aimed to assess serum AMH levels in girls with TS and its relation to karyotype, spontaneous puberty, and growth hormone (GH) therapy. Fifty TS were compared to 50 age- and sex-matched controls. All subjects were subjected to history, anthropometric assessment, Tanner pubertal staging and measurement of serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and AMH. Karyotype results were obtained from patients' records. Serum AMH was measurable in 12 TS patients (24%). The lowest frequency of measurable AMH was in patients with a karyotype of 45,X. The measurable AMH was associated with spontaneous breast development (p = .003) and spontaneous menarche (p = .001). AMH correlated negatively with FSH (r = -.846, p = .000) and LH (r = -.83, p = .034). GH therapy increased the odds of having measurable AMH in TS girls (p = .002). In conclusion, AMH was associated with karyotype, spontaneous pubertal development, LH, and FSH in TS girls and may serve as a useful marker of ovarian function and ongoing follicular development in prepuberty.

Vitamin D status in prepubertal children with isolated idiopathic growth hormone deficiency: effect of growth hormone therapy.

Few studies, and with controversial results, analyzed vitamin D status in children before and after growth hormone (GH) treatment. Thus, we aimed to assess vitamin D status in prepubertal children with idiopathic growth hormone deficiency (GHD), and to evaluate the effect of GHD and GH treatment on vitamin D levels. Fifty prepubertal children with isolated GHD were compared with 50 controls. All were subjected to history, anthropometric assessment and measurement of 25 hydroxyvitamin D (25(OH)D), serum calcium, phosphorous, alkaline phosphatase and parathyroid hormone (PTH) at diagnosis and 1 year after GH therapy. Serum 25(OH)D levels <30 ng/mL and 20 ng/mL were defined as vitamin D insufficiency and deficiency, respectively. 25(OH)D was lower in cases than controls. Forty per cent of children with GHD were 25(OH)D insufficient and 44% deficient, while 16% were sufficient at baseline. There was a positive correlation between 25(OH)D and peak GH levels. Peak GH was a significant predictor of 25(OH)D levels. After 1 year of GH therapy, 25(OH)D increased (18.42±5.41 vs 34.5±10.1 ng/mL; P<0.001). Overall, 22% of cases remained insufficient and 24% deficient, with an increase in prevalence of children with normal levels (54%; P<0.001). 25(OH) correlated negatively with PTH (r=-0.71, P=0.01). In conclusion, hypovitaminosis D is prevalent in children with GHD and significantly improved 1 year after GH therapy. 25(OH)D should be assessed in children with GHD at diagnosis and during follow-up.

Serum Chemerin in Obese Children and Adolescents Before and After L-Carnitine Therapy: Relation to Nonalcoholic Fatty Liver Disease and Other Features of Metabolic Syndrome.

BACKGROUND AND AIMS: Chemerin plays an important role in metabolic syndrome (MetS) including nonalcoholic fatty liver disease (NAFLD). L-carnitine (LC) may reduce plasma glucose, lipid profile, and improve liver function. The aim of the study was to assess serum chemerin in obese children with suspected NAFLD, the effect of LC on NAFLD grade, chemerin and metabolic profile. METHODS: Fifty obese children were compared to 50 controls. All were subjected to anthropometric assessment, liver function, fasting lipid profile, glucose/insulin (G/I) ratio, homeostasis model assessment (HOMA) index, serum chemerin and abdominal ultrasonography before and after LC. RESULTS: Serum chemerin was higher in cases than controls. Eighty percent of cases had NAFLD with increase in chemerin as severity of NAFLD increased. There was a decrease in frequency of NAFLD and its severity after LC therapy. CONCLUSIONS: Noninvasive monitoring of serum chemerin in obese patients with suspected NAFLD could be used to diagnose NAFLD. LC supplementation is effective in treatment of NAFLD and reducing chemerin.

Iron homeostasis and serum hepcidin-25 levels in obese children and adolescents: relation to body mass index.

BACKGROUND/AIMS: The etiology of the hypoferremia of obesity is unclear. Hepcidin is the body's main regulator of systemic iron (Fe) and has been reported to be elevated in obese patients. Thus, we aimed to assess Fe status and serum hepcidin-25 levels and their relationship with body mass index (BMI) in obese Egyptian children and adolescents. METHODS: Fifty obese children were compared to 50 age-, sex- and pubertal stage- matched controls. All subjects were subjected to history and anthropometric assessment and measurement of serum Fe, total iron binding capacity (TIBC), ferritin, transferrin saturation (TS), soluble transferrin receptor (sTfR) and hepcidin. RESULTS: Fe, TS and TIBC were lower, while ferritin, sTfR and hepcidin-25 were higher in obese patients than controls. BMI standard deviation score (SDS) correlated negatively with Fe (r = -0.82, p < 0.01), TS (r = -0.79, p = 0.02) and TIBC (r = -0.69, p = 0.02), and positively with ferritin (r = +0.73, p < 0.001), sTfR (r = +0.80, p < 0.01) and hepcidin (r = +0.95, p < 0.001). Higher BMI SDS and hepcidin were risk factors for iron deficiency (ID). CONCLUSIONS: Hypoferremia and elevated hepcidin-25 are prevalent in obese children and correlated with BMI SDS. The connection between hepcidin and inflammation could explain the association of ID with obesity.

R620W polymorphism of protein tyrosine phosphatase PTPN22 in Egyptian children and adolescents with systemic lupus erythematosus: relation to thyroid autoimmunity.

BACKGROUND: Some studies showed associations of the minor T allele of the C1858T single nucleotide polymorphism (SNP) corresponding to the R620W amino acid substitution of protein tyrosine phosphatase (PTPN22) with multiple autoimmune diseases, including systemic lupus erythematosus (SLE). OBJECTIVES: To study the frequency of PTPN22 R620W polymorphism among Egyptian patients with SLE and to test the association of the T allele with autoimmune thyroid disease in such patients. METHODS: Clinical evaluation, measurement of thyroid hormones and antibodies, and genotyping of PTPN22 R620W polymorphism were done for 60 SLE patients and 60 age- and sex-matched healthy subjects. RESULTS: Nineteen SLE cases (31.67%) had thyroid dysfunction with subclinical hypothyroidism being the most frequent form of thyroid dysfunction (20%) followed by primary hypothyroidism (6.67%), subclinical hyperthyroidism (3.33%) and primary hyperthyroidism (1.67%). Autoimmune thyroid disease was detected in 36.67% of cases. Systemic lupus erythematosus disease activity index (SLEDAI) score did not differ between patients with thyroid dysfunction and euthyroid patients (p=0.061) nor with the frequency of positive thyroid peroxidise antibodies (TPOAb, p=0.092) and antithyroglobulin antibodies (ATGAb, p=0.1). T allele frequency did not differ between cases and controls (p=1.19) and was associated with autoimmune thyroid disease in Egyptian SLE patients (p=0.002). CONCLUSIONS: R620W polymorphism of the PTPN22 gene is not a major risk allele for SLE susceptibility among Egyptian SLE patients but appears to be a risk factor for concurrent autoimmune thyroid disease and SLE.

Vitamin D status and scholastic achievement in middle age childhood.

Non-classical effects of vitamin D are not surprising in that many tissues, including neurons, possess vitamin D receptors. Thirty school aged children with delayed scholastic achievement and 15 normal ones were enrolled in the current study to identify the serum 25-hydroxy vitamin D [25(OH) D] status in school aged children in relation to their scholastic achievement. Besides estimation of serum 25(OH) D levels, neuro-developmental assessment was done using the Wechsler Intelligence Scale for Children (WISC) and the Benton's Visual Retention Test (BVRT). Serum 25(OH) D was significantly lower in children with delayed scholastic achievement. Picture completion scores were significantly lower in children with deficient and inadequate serum 25(OH) D. There were positive correlations between serum 25(OH) D level and values of WISC. Regarding BVRT results, good memory was associated with adequate serum 25(OH) D. In conclusion, serum 25(OH) D is deficient in children with delayed scholastic achievement causing affection of memory and learning process. Larger scale studies using learning assessment tools are thus recommended to further prove this point and search the impact of vitamin D supplementation on the school achievement in this age group.

Effect of zinc supplementation on growth hormone-insulin growth factor axis in short Egyptian children with zinc deficiency.

BACKGROUND: The relationship between zinc (Zn) and growth hormone-insulin growth factor (GH-IGF) system and how Zn therapy stimulates growth in children has not been clearly defined in humans. Thus, we aimed to assess GH-IGF axis in short children with Zn deficiency and to investigate the effect of Zn supplementation on these parameters. METHODS: Fifty pre-pubertal Egyptian children with short stature and Zn deficiency were compared to 50 age-, sex-, and pubertal stage- matched controls. All subjects were subjected to history, auxological assessment and measurement of serum Zn, IGF-1, insulin growth factor binding protein-3 (IGFBP-3); and basal and stimulated GH before and 3 months after Zn supplementation (50 mg/day). RESULTS: After 3 months of Zn supplementation in Zn-deficient patients, there were significant increases in height standard deviation score (SDS, P = 0.033), serum Zn (P < 0.001), IGF-1 (P < 0.01), IGF-1 standard deviation score (SDS, P < 0.01) and IGFBP-3 (P = 0.042). Zn rose in all patients but reached normal ranges in 64 %, IGF-1 levels rose in 60 % but reached normal ranges in 40 % and IGFBP-3 levels rose in 40 % but reached reference ranges in 22 %. Growth velocity (GV) SDS did not differ between cases and controls (p = 0.15) but was higher in GH-deficient patients than non-deficient ones, both having Zn deficiency (p = 0.03). CONCLUSION: Serum IGF-1 and IGFBP-3 levels were low in short children with Zn deficiency, and increased after Zn supplementation for 3 months but their levels were still lower than the normal reference ranges in most children; therefore, Zn supplementation may be necessary for longer periods.

Reduced serum concentrations of 25-hydroxy vitamin D in Egyptian patients with systemic lupus erythematosus: relation to disease activity.

BACKGROUND: Recently, vitamin D deficiency has been implicated as a potential environmental factor triggering some autoimmune disorders, including systemic lupus erythematosus (SLE)). In addition, patients with SLE, especially those with increased disease activity, were suggested to have decreased vitamin D level, suggesting that vitamin D might play a role in regulating autoantibody production. MATERIAL/METHODS: To assess 25 hydroxy vitamin D [25(OH)D] status in Egyptian patients with SLE and its relation to disease activity. Clinical evaluation and assay of serum 25(OH)D, total calcium, phosphorous, alkaline phosphatase (ALP) and parathyroid hormone (PTH) were done on 60 SLE patients in comparison to 60 matched-healthy subjects. Serum 25(OH)D levels <30 and 10 ng/ml were defined as vitamin D insufficiency and deficiency, respectively. RESULTS: Serum 25(OH)D was significantly lower in patients than in controls (26.33 ± 12.05 vs. 42.66 ± 9.20 respectively, p < 0.0001), with 13.30% and 60% being deficient and insufficient, respectively. Serum 25(OH)D levels were lower with increased disease activity (p = 0.03) and frequency of photosensitivity(p = 0.02) and photoprotection (p = 0.002). Systemic lupus erythematosus disease activity index (SLEDAI) score (OR: 2.72, 95% CI: 1.42-5.18, P = 0.002), photosensitivity (OR: 3.6, 95% CI: 1.9-6.8, P < 0.01) and photoprotection (OR: 6.7, 95% CI: 2.9-8.8, P < 0.001) were significant predictors of 25(OH)D level among SLE cases. CONCLUSIONS: Low vitamin D status is prevalent in Egyptian SLE patients despite plentiful exposure to sunlight throughout the year, and its level is negatively correlated to disease activity. Future studies looking at a potential role of vitamin D in the pathophysiology and treatment of SLE are warranted.

Growth hormone deficiency in children and adolescents with cerebral palsy: relation to gross motor function and degree of spasticity.

Children with Cerebral Palsy (CP) often have poor linear growth during childhood with short final height. Thus, we aimed to assess serum growth hormone (GH), insulin like growth factor-1 (IGF-1) and insulin like growth factor binding protein-3 (IGFBP-3) levels among CP patients and their relation to each of gross motor function and degree of spasticity. Fifty CP children and adolescents were studied in comparison to 50 healthy age-, sex- and pubertal stage-matched children and adolescents. All subjects were subjected to clinical evaluation, Intelligence Quotient (IQ) assessment and measurement of serum GH, IGF-1 and IGFBP-3. All auxological and hormonal parameters were significantly lower among cases. Fifty two% of cases were GH-deficient and 62% had reduced IGF-land IGFBP-3 levels. Gross Motor Function Measure- 88 (GMFM-88) score correlated negatively with each of basal (r = -0.71, p = 0.02) and peak stimulated GH (r =-0.88, p = <0.001); IGF-1 (r = -0.64, p = 0.04) and IGFBP-3 (r = -0.69, p = 0.031). There were significant negative correlations between the degree of spasticity assessed by Modified Ashworth Scale and each of basal (r = -0.61, p = 0.032) and peak stimulated GH (r = -0.78, p = 0.01); IGF-1 (r = -0.65, p = 0.041) and IGFBP-3 (r = -0.62, p = 0.035). Growth Hormone Deficiency (GHD) is prevalent in children with CP and could be one of the causes of their short stature.