RESUMO
BACKGROUND: Community-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. OBJECTIVES: To evaluate the association of the VDR gene Fok I polymorphism with susceptibility to CAP in Egyptian children. METHODS: This 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. RESULTS: The 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. CONCLUSION: The VDR gene Fok I (rs2228570) polymorphism confers susceptibility to CAP in Egyptian children.
Assuntos
Infecções Comunitárias Adquiridas/genética , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Predisposição Genética para Doença , Pneumonia/genética , Polimorfismo Genético , Receptores de Calcitriol/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/sangue , Egito , Feminino , Humanos , Lactente , Masculino , Pneumonia/sangue , Estudos Prospectivos , Vitamina D/análogos & derivados , Vitamina D/sangueRESUMO
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 -31â(C/T), and -511â(C/T) of interleukin-1beta (IL-1ß) 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-1ß 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-1ß promoter at positions -31â(C/T), -511â(C/T), and IL-1RA gene VNTR polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while the serum IL-1ß levels were measured by enzyme-linked immunosorbent assay (ELISA) method.The frequency of the IL-1ß-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; Pâ=â0.001 for the TT genotype and OR: 1.65; 95% CI: 1.18-2.3; Pâ=â0.003 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; Pâ=â0.001and OR: 1.73; 95% CI: 1.24-2.4; Pâ=â0.001, 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; Pâ=â0.001) and (OR: 1.94; 95% CI: 1.3-2.8 for the allele II; Pâ=â0.001, respectively). Carriers of the IL-1RA II/II homozygous variant and allele II had significantly higher serum levels of IL-1ß 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-1ß promoter and IL-1RA II/II genotype constitute risk factors for developing FS in Egyptian children.
Assuntos
Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-1beta/genética , Convulsões Febris/genética , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Egito/epidemiologia , Feminino , Genótipo , Humanos , Lactente , Masculino , Razão de Chances , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genéticaRESUMO
BACKGROUND: Juvenile 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. METHODS: This 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. RESULTS: Compared 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. CONCLUSION: We 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.
Assuntos
Artrite Juvenil/diagnóstico , Artrite Juvenil/genética , Interleucina-10/genética , Mutação , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Alelos , Artrite Juvenil/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Egito , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Interleucina-10/sangue , Masculino , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: 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. OBJECTIVES: In this study, we aimed to investigate whether the ACE insertion/deletion (I/D) polymorphism (rs4340) could be a genetic marker for CAP susceptibility in Egyptian children, and we also measured the serum ACE level to assess its relation to such polymorphism. METHODS: This was a prospective case-control study included 300 patients with CAP, and 300 age, gender, and ethnicity matched healthy controls. The ACE I/D polymorphism (rs4340) at intron 16 was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while the serum ACE levels were measured by ELISA. RESULTS: Compared to the controls subjects, the frequencies of the ACE DD genotype and D allele were overrepresented in patients with CAP (OR = 3.05; [95%CI: 2.14-4.35] for the DD genotype; P < 0.001) and (OR: 1.8; [95%CI: 1.42-2.29]; for the D allele; P < 0.01, respectively). Patients with the DD genotype had significantly higher mean serum ACE levels (45.6 ± 11.4 U/L) compared to those with ID genotype (36.5 ± 8.3 U/L) and II genotype (21.6 ± 5.7 U/L); P < 0.01, respectively. CONCLUSION: The ACE I/D polymorphism (rs4340) may contribute to the genetic susceptibility of CAP in Egyptian children. The ACE D allele and DD genotype were associated with higher serum ACE levels among studied CAP patients.
Assuntos
Infecções Comunitárias Adquiridas/genética , Peptidil Dipeptidase A/genética , Pneumonia/genética , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/epidemiologia , Egito/epidemiologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Peptidil Dipeptidase A/sangue , Pneumonia/sangue , Pneumonia/epidemiologia , Reação em Cadeia da Polimerase , Polimorfismo Genético , Estudos ProspectivosRESUMO
Community-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; Pâ<â0.01) and (70%; OR: 1.95; 95% CI: 1.27-3.00 for the A allele; Pâ<â0.01, respectively). We found that patients with the GG genotype had significantly higher serum IL-10 levels (46.7â±â9.5âpg/mL) compared to those with AG genotype (21.8â±â4.5âpg/mL) and AA genotype (11.5â±â3.3âpg/mL); Pâ<â0.01, 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; Pâ<â0.01).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.
Assuntos
Interleucina-10/genética , Pneumonia Bacteriana/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/genética , Egito , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Interleucina-10/sangue , Masculino , Estudos ProspectivosRESUMO
Systemic 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; Pâ=â0.002 and OR: 1.84; 95% CI: 1.21-2.80; Pâ=â0.003; respectively). We found a significant association between VDR BsmI BB genotype with lupus nephritis (OR: 6.8; 95% CI: 1.18-50.5; Pâ=â0.001). 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 Pâ>â0.05).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.
Assuntos
Lúpus Eritematoso Sistêmico/genética , Polimorfismo Genético , Receptores de Calcitriol/genética , Adolescente , Estudos de Casos e Controles , Criança , Egito , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Masculino , Estudos Prospectivos , Vitamina D/análogos & derivados , Vitamina D/sangueRESUMO
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: Genotype 4 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.
Assuntos
Hepacivirus/genética , Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/imunologia , Hepatite C Crônica/imunologia , RNA Viral/genética , Adolescente , Biópsia , Criança , Pré-Escolar , Feminino , Seguimentos , Genótipo , Hepatite C Crônica/genética , Hepatite C Crônica/virologia , Humanos , Fígado/patologia , Fígado/virologia , Masculino , Prevalência , Estudos ProspectivosRESUMO
This study determined the prevalence of seropositivity of anti-H. pylori IgG antibodies, and evaluated some socio-epidemiologic characteristics among family members of infected and non-infected symptomatic children. One hundred children with upper gastrointestinal symptoms without previous H. pylori eradication treatment were prospectively studied by both upper endoscopy with histopathological biopsies examination, and serum anti-H. pylori IgG test between July 2012 to June 2013. The patients were subdivided into: H. pylori infected children (GI), and H. pylori non-infected children (GII). Also, 320 of their family members were examined for serum anti-H. pylori IgG and stool antigen tests. Sheets were filled out included personal and medical history. The results showed statistically significant difference between both groups as regard dyspepsia, anemia, and histopathological findings (chronic active gastritis, peptic ulcer, and duodenitis). Family members were subdivided into: those of H. pylori infected symptomatic children (165) and those of H. pylori non-infected symptomatic children (155). Anti-H. pylori IgG prevalence was significantly higher in relatives of GI than those of GII (69.1% vs. 29%; p<0.05). The seroprevalence of H.pylori infection in all family members was (49.7%). Mothers of GI showed the highest seroprevalence (39.5%) as compared to fathers and siblings (22.8%, & 37.7%, respectively). Relatives of GI with low socioeconomic status, and lived in rural area showed the highest seroprevalence (82.5%, & 78.1% respectively).