Mohammed E. Hamed

Vitamin D receptor gene BsmI polymorphisms in Egyptian children and adolescents with systemic lupus erythematosus: A case-control study.

AbstractSystemic lupus erythematosus (SLE) is a multisystemic autoimmune disease. The vitamin D receptor (VDR) gene is a candidate gene for susceptibility to autoimmune disorders. To date, only a few studies concerned the association of the VDR gene polymorphisms with childhood-onset SLE.In this study, we aimed to investigate the BsmI polymorphisms in the VDR gene, for the first time in Egyptian children and adolescents with SLE, to determine whether this polymorphism could be a marker of susceptibility to or severity of SLE and we also measured the serum level of 25-hydroxyvitamin D (25[OH] D) to assess its relation to such polymorphism.This was a case–control study including 100 patients with SLE and matched with age, sex, and ethnicity and 100 healthy controls. All subjects were genotyped for the VDR gene BsmI polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), whereas the serum 25(OH) D levels were measured by enzyme-linked immunosorbent assay method.Compared to the contros subjects, the VDR BsmI BB genotype and B allele were overrepresented among SLE patients (odda ratio [OR]: 5.5; 95% confidence interval [CI]: 1.9–15.9; P = 0.002 and OR: 1.84; 95% CI: 1.21–2.80; P = 0.003; respectively). We found a significant association between VDR BsmI BB genotype with lupus nephritis (OR: 6.8; 95% CI: 1.18–50.5; P = 0.001). However, we did not observe any significant association of studied polymorphisms with other clinical manifestations, laboratory profiles of SLE, or disease activity score. Our data revealed no association between VDR BsmI genotypes or alleles and serum 25-hydroxyvitamin D levels among studied patients with SLE (all P > 0.05).We demonstrate for the first time, to the best of our knowledge, that the VDR BsmI gene polymorphisms may contribute to susceptibility to SLE in Egyptian children and adolescents. Moreover, we found that the BB genotype constituted a risk factor for the development of nephropathy among studied patients with SLE. However, we did not find any significant association of the VDR BsmI gene variants with other clinical manifestations, laboratory profiles of SLE, disease activity index score, or serum 25-hydroxyvitamin D levels.

Interleukin-10 -1082 G/A gene polymorphisms in Egyptian children with CAP: A case-control study.

AbstractCommunity-acquired pneumonia (CAP) is one of the leading causes of death worldwide. Cytokines are involved in the pathogenesis of CAP. To date, only a few studies concerned the association of interleukin-10 (IL-10) gene polymorphisms with CAP.In this study, we aimed to investigate whether the -1082(G/A) polymorphism in the promoter region of the IL-10 gene is involved in susceptibility to and the outcome of CAP, and we also measured the serum level of IL-10 to assess its relation to such polymorphism.This was a case–control study included 100 patients with CAP, and matched with age, gender, and ethnicity of 100 healthy control children. IL-10 -1082(G/A) gene polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism, while the serum IL-10 levels were measured by ELISA method.Compared to the controls subjects, the frequencies of the IL-10 -1082 AA genotype and A allele were observed to be overrepresented in patients with CAP (51%; odds ratio [OR] = 2.8; 95% confidence interval [CI]: 1.5–5.3 for the AA genotype; P < 0.01) and (70%; OR: 1.95; 95% CI: 1.27–3.00 for the A allele; P < 0.01, respectively). We found that patients with the GG genotype had significantly higher serum IL-10 levels (46.7 ± 9.5 pg/mL) compared to those with AG genotype (21.8 ± 4.5 pg/mL) and AA genotype (11.5 ± 3.3 pg/mL); P < 0.01, respectively. Our data revealed a significant positive association between the -1082 GG genotype and susceptibility to severe sepsis, acute respiratory failure, and hospital mortality (OR: 3.8; 95% CI: 1.3–11.2; P < 0.01).We demonstrate for the first time, to the best of our knowledge, that IL-10 -1082 (G/A) gene polymorphism may contribute to susceptibility to CAP in Egyptian children. Moreover, we observed that the presence of a G allele or GG genotype at the -1082 position of the promoter region of the IL-10 gene constitute risk factors for developing severe sepsis, acute respiratory failure, and hospital mortality among patients with CAP.

Study of non-organ-specific antibodies in children with Genotype 4 chronic Hepatitis C

Background/Aim: Adult studies established a relationship between hepatitis C virus (HCV) infection and the presence of non–organ-specific antibodies (NOSAs). Most studies were carried out on genotypes 1 and 2. Only a few studies addressed that issue in pediatrics. No studies have been carried out on autoimmunity and genotype 4 in children. We aim to investigate NOSAs in 80 Egyptian children with chronic HCV infection along with studying the underlying genotype of HCV, and correlating autoimmunity with the epidemiological, clinical, biochemical, and virological features. Materials and Methods: HCV-RNA was assayed by the polymerase chain reaction and viral genotypes were determined. NOSAs were measured and liver biopsies were taken for histopathological examination. Results: Genotype4 was the only detected genotype in the included 80 patients. Anti-smooth muscle antibodies (ASMA) were the only detected antibodies in 32 (40%) patients, always with V specificity (vessels only) at titers ranging from 1:20 and 1:160. Anti-nuclear antibodies (ANA) and liver–kidney microsomal antibodies-1 (LKMA-1) were not detected in any of our patients. Epidemiologic and clinical features did not significantly differ between autoantibody-positive and -negative patients. Among biochemical features, significantly high levels of total bilirubin, albumin, immunoglobulins, alkaline phosphatase, and gamma-glutamyl transpeptidase were found in the antibody-positive group. Conclusion: Genotype 4 HCV is the prevailing genotype in Egyptian children with chronic HCV infection. A consistent proportion of these children with chronic HCV infection circulate non–organ-specific autoantibodies. The prevalence of ASMA and the absence of ANA and LKMA-1 might be related to the unique situation in Egypt with unique prevalence of genotype 4. More studies are warranted on larger pediatric population to validate these findings.

Angiotensin‐converting enzyme insertion/deletion gene polymorphism in Egyptian children with CAP: A case‐control study

Community‐acquired pneumonia (CAP) is a major cause of childhood morbidity and mortality worldwide. The angiotensin‐converting enzyme (ACE) gene is a potential candidate gene for CAP risk.

Interleukin-1β and interleukin-1receptor antagonist polymorphisms in Egyptian children with febrile seizures: A case-control study

Abstract Febrile seizure is the most common seizure disorder of childhood. Of the pro-inflammatory cytokines, interleukin-1 is defined as the first endogenous pyrogen. We designed this study to investigate single-nucleotide polymorphisms (SNPs) situated at positions –31 (C/T), and –511 (C/T) of interleukin-1beta (IL-1&bgr;) gene promoter and interleukin-1receptor antagonist (IL-1RA) gene variable number of tandem repeats in intron 2 (VNTR); to determine whether these polymorphisms could be a marker of susceptibility to febrile seizures in Egyptian children and we also measured the serum level of IL-1&bgr; to assess its relation to such polymorphisms. This was a case-control study included 155 patients with febrile seizure, and matched with age, sex, ethnicity 155 healthy control subjects. IL-1&bgr; promoter at positions −31 (C/T), −511 (C/T), and IL-1RA gene VNTR polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while the serum IL-1&bgr; levels were measured by enzyme-linked immunosorbent assay (ELISA) method. The frequency of the IL-1&bgr;-511 TT genotype and T allele at the same position were observed to be increased in patients with febrile seizures (FS) compared with the control group (odds ratio [OR]: 3.96; 95% confidence interval [CI]: 1.68–9.5; P = 0.001 for the TT genotype and OR: 1.65; 95% CI: 1.18–2.3; P = 0.003 for the T allele, respectively). The IL-1 RA II/II homozygous variant and IL-1 RA allele II were overrepresented in patients with FS than control group (OR: 4.02; 95% CI: 1.78–9.15; P = 0.001and OR: 1.73; 95% CI: 1.24–2.4; P = 0.001, respectively). We found a significant positive association between the IL-1 RA II/II genotype and susceptibility to FS in sporadic cases as did allele II at the same position (OR: 5.04; 95% CI: 2.1–12.5 for the IL-1 RA II/II genotype; P = 0.001) and (OR: 1.94; 95% CI: 1.3–2.8 for the allele II; P = 0.001, respectively). Carriers of the IL-1RA II/II homozygous variant and allele II had significantly higher serum levels of IL-1&bgr; compared with those with other genotypes and alleles. We demonstrate for the first time that the presence of a T allele or TT genotype at -511 of IL-1&bgr; promoter and IL-1RA II/II genotype constitute risk factors for developing FS in Egyptian children.

Association of IL-10 gene polymorphisms and susceptibility to Juvenile Idiopathic Arthritis in Egyptian children and adolescents: a case-control study

BackgroundJuvenile Idiopathic Arthritis (JIA) is the most common chronic arthritis in children worldwide. Among anti-inflammatory cytokines, interleukin-10 (IL-10) is a key immunosuppressive cytokine involved in the pathogenesis of JIA. To date, only a few studies concerned the association of interleukin-10 gene polymorphisms with JIA. In this study, we aimed to investigate 3 cytokine single-nucleotide polymorphisms situated at positions -1082(G/A), −819(C/T), and −592(C/A) in the promoter region of the IL-10 gene to determine whether this polymorphism could be a marker of susceptibility to JIA in Egyptian children and adolescents. We also measured the serum level of IL-10 to assess its relation to such polymorphism.MethodsThis was a case-control study included 100 patients diagnosed with JIA, and matched with age, gender, ethnicity 100 healthy control subjects.Interleukin-10 −1082(G/A), −819(C/T), and −592(C/A) polymorphisms were genotyped by amplification refractory mutation system- polymerase chain reaction (ARMS)-PCR methodology, while the serum IL10 levels were measured by ELISA method.ResultsCompared to the controls subjects, the frequency of IL-10- AA genotype and A allele at the –1082 position were overrepresented in patients with JIA (OR = 2.7; 95% CI: 1.1–6.4 for the AA genotype; P <0.05 and OR: 1.5; 95% CI: 1.03–2.3 for the A allele; P <0.05 respectively). On the other hand, no significant differences were found between the 2 groups in the genotype or allele frequencies for the –819 and –592 positions. Of note, we found a significant positive association between the IL-10 (-1082) AA genotype and susceptibility to polyarticular JIA (OR: 4.3; 95% CI: 1.5–12.7; P <0.01). We observed that patients with the IL-10 (-1082) AA genotype had significantly lower serum IL-10 levels (2.3 ± 0.9 pg/ml) compared to those with AG genotype (7.6 ± 1.5 pg/ml) and GG genotype (9.5 ± 1.2 pg/ml); P < 0.01, respectively.ConclusionWe demonstrate for the first time, to the best of our knowledge, that the presence of an A allele or AA gene variant at the –1082 position of the promoter region of the interleukin-10 gene may constitute risk factors for developing JIA in Egyptian children and adolescents. Moreover, we observed a significant positive association between the IL10 –1082 AA gene variant and susceptibility to polyarticular JIA.

Association of vitamin D receptor gene FokI polymorphism and susceptibility to CAP in Egyptian children: a multicenter study

BackgroundCommunity-acquired pneumonia (CAP) is the leading cause of child deaths around the world. Recently, the vitamin D receptor (VDR) gene has emerged as a susceptibility gene for CAP.ObjectivesTo evaluate the association of the VDR gene Fok I polymorphism with susceptibility to CAP in Egyptian children.MethodsThis was a multicenter case-control study of 300 patients diagnosed with CAP, and 300 well-matched healthy control children. The VDR Fok I (rs2228570) polymorphism was genotyped by PCR-restriction fragment length polymorphism (RFLP), meanwhile serum 25-hydroxy vitamin D (25D) level was assessed using ELISA method.ResultsThe frequencies of the VDR FF genotype and F allele were more common in patients with CAP than in our control group (OR = 3.6; (95% CI: 1.9–6.7) for the FF genotype; P = 0.001) and (OR: 1.8; (95% CI: 1.4–2.3) for the F allele; P = 0.01). Patients carrying the VDR FF genotype had lower serum (25D) level (mean; 14.8 ± 3.6 ng/ml) than Ff genotype (20.6 ± 4.5 ng/ml) and the ff genotype (24.5 ± 3.7 ng/ml); P < 0.01.ConclusionThe VDR gene Fok I (rs2228570) polymorphism confers susceptibility to CAP in Egyptian children.

Risk Factors of Type 1 Diabetes Mellitus among Egyptian Infants: A Case-Control Study

Diabetes mellitus is a metabolic disease characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The chronic hyperglycemia of diabetes is associated with long term damage, dysfunction and failure of various organs, especially the eye, kidney, nerves and blood vessels.1 The onset of type 1 diabetes before the first year of age is a rare condition and is probably due to an interaction between genetic and environmental factors, which together may explain such an early event.2

Study of non-organ-specific antibodies in Egyptian children with genotype-4 chronic hepatitis C

Background/rationale Adult studies established a relationship between hepatitis C virus (HCV) infection and the presence of anti-nuclear antibodies (ANA), anti-smooth-muscle antibodies (ASMA), and anti-liver–kidney-microsomal type 1 antibodies (LKMA-1). No studies have been carried out on autoimmunity and genotype-4 in children. We aimed to investigate non-organ-specific autoantibodies in Egyptian children with chronic HCV infection and to correlate autoimmunity with epidemiological, clinical, biochemical, and virological features. Methods All enrolled patients (n=80) were positive for anti-HCV antibodies. HCV-RNA was assayed by PCR and viral genotypes were determined. ANA, ASMA, and LKMA-1 levels were assessed and liver biopsies were taken for histopathological examination. Results Genotype 4 was the only detected genotype in our cohort. ASMA were the only detected autoantibodies; they were detected in 32 patients (40%), always with V specificity (vessels only) at titers ranging from 1 : 20 to 1 : 160. ANA and LKMA-1 were not detected in any of our patients. Epidemiologic and clinical features did not significantly differ between autoantibody-positive and autoantibody-negative patients. Among biochemical features, significantly high levels of total bilirubin, albumin, immunoglobulins, alkaline phosphatase, and &ggr;-glutamyl transpeptidase were found in the antibody-positive group. Conclusion Genotype-4 HCV is the prevailing genotype in Egyptian children with chronic HCV infection. A consistent proportion of these children with chronic HCV infection have non-organ-specific autoantibodies in their circulatory system. The prevalence of ASMA and the absence of ANA and LKMA-1 might be related to the unique situation in Egypt of unique prevalence of genotype 4. More studies are warranted in larger pediatric populations to validate these findings.

Anti-soluble liver antigen prevalence in chronic hepatitis

Objective This study was conducted to determine the prevalence of antibodies against soluble liver antigen (SLA) in children with chronic hepatitis including autoimmune hepatitis (AIH), giant cell hepatitis, and chronic hepatitis C. Patients and methods Data were collected in a cross-sectional study of 40 children with chronic hepatitis including AIH (n=15), giant cell hepatitis (n=10), and chronic hepatitis C (n=15) between January 2010 and February 2011. AIH patients were diagnosed according to international diagnostic criteria for the diagnosis of AIH. Giant cell hepatitis patients were diagnosed on the basis of liver biopsy. Chronic hepatitis C patients were diagnosed on the basis of a serological assay for antibodies against hepatitis C virus and molecular assay for hepatitis C virus RNA detection and quantification. Autoantibodies such as antinuclear antibodies, anti-smooth muscle antibodies, anti-liver kidney microsomal type 1, and anti-SLA were tested. Results The prevalence of autoantibodies antinuclear antibodies, anti-smooth muscle antibodies, anti-SLA, and anti-liver kidney microsomal type 1 in the AIH group was 4/15 (26.7%), 11/15 (73.3%), 10/15 (66.7%), and 0/15 (0%), respectively, that in the giant cell hepatitis group was 0/10 (0%) for all, and prevalence in the chronic hepatitis C group was 0/15 (0%), 5/15 (33.3%), 3/15 (20%), and 0/15 (0%), respectively. Anti-SLA as a marker for AIH had a sensitivity and specificity of 66.7 and 92.5%, respectively. The highest median value of anti-SLA was present in AIH patients (35.2 AU). Conclusion Anti-SLA antibodies have a significant prevalence in children with AIH and chronic hepatitis C, but have no significant value in children with giant cell hepatitis.